請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/3991
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 楊雅雯 | |
dc.contributor.author | Kai-Wen Cheng | en |
dc.contributor.author | 鄭凱文 | zh_TW |
dc.date.accessioned | 2021-05-13T08:39:58Z | - |
dc.date.available | 2021-02-26 | |
dc.date.available | 2021-05-13T08:39:58Z | - |
dc.date.copyright | 2016-02-26 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-02-04 | |
dc.identifier.citation | 1. Guy, B. 2007. The perfect mix: recent progress in adjuvant research. Nat Rev Micro 5: 505-517.
2. Awate, S., L. A. Babiuk, and G. Mutwiri. 2013. Mechanisms of action of adjuvants. Frontiers in Immunology 4: 114. 3. Petrovsky, N., and J. C. Aguilar. 2004. Vaccine adjuvants: current state and future trends. Immunol Cell Biol 82: 488-496. 4. Shen, S.-S., and Y.-W. Yang. 2015. Dynamics of antigen delivery and the functional roles of L121-adjuvant. Vaccine 33: 4341-4348. 5. Hariharan, K., and N. Hanna. 1998. Development and application of PROVAX™ adjuvant formulation for subunit cancer vaccines. Advanced Drug Delivery Reviews 32: 187-197. 6. Byars, N. E., and A. C. Allison. 1987. Adjuvant formulation for use in vaccines to elicit both cell-mediated and humoral immunity. Vaccine 5: 223-228. 7. Kenney, J. S., B. W. Hughes, M. P. Masada, and A. C. Allison. 1989. Influence of adjuvants on the quantity, affinity, isotype and epitope specificity of murine antibodies. Journal of Immunological Methods 121: 157-166. 8. Raychaudhuri, S., M. Tonks, F. Carbone, T. Ryskamp, W. J. Morrow, and N. Hanna. 1992. Induction of antigen-specific class I-restricted cytotoxic T cells by soluble proteins in vivo. Proceedings of the National Academy of Sciences 89: 8308-8312. 9. Hsu, F. J., C. B. Caspar, D. Czerwinski, L. W. Kwak, T. M. Liles, A. Syrengelas, B. Taidi-Laskowski, and R. Levy. 1997. Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma — long-term results of a clinical trial. Blood 89: 3129-3135. 10. Allison, A. C. 1999. Squalene and squalane emulsions as adjuvants. Methods 19: 87-93. 11. Allison, A. C., and N. E. Byars. 1986. An adjuvant formulation that selectively elicits the formation of antibodies of protective isotypes and of cell-mediated immunity. Journal of Immunological Methods 95: 157-168. 12. Hunter, R., F. Strickland, and F. Kézdy. 1981. The adjuvant activity of nonionic block polymer surfactants. I. The role of hydrophile-lipophile balance. The Journal of Immunology 127: 1244-1250. 13. Seita, J., and I. L. Weissman. 2010. Hematopoietic stem cell: self-renewal versus differentiation. Wiley interdisciplinary reviews. Systems biology and medicine 2: 640-653. 14. Bryder, D., D. J. Rossi, and I. L. Weissman. 2006. Hematopoietic stem cells: the paradigmatic tissue-specific stem cell. The American Journal of Pathology 169: 338-346. 15. Weissman, I. L., and J. A. Shizuru. 2008. The origins of the identification and isolation of hematopoietic stem cells, and their capability to induce donor-specific transplantation tolerance and treat autoimmune diseases. Blood 112: 3543-3553. 16. Ikuta, K., and I. L. Weissman. 1992. Evidence that hematopoietic stem cells express mouse c-kit but do not depend on steel factor for their generation. Proceedings of the National Academy of Sciences of the United States of America 89: 1502-1506. 17. Spangrude, G., S. Heimfeld, and I. Weissman. 1988. Purification and characterization of mouse hematopoietic stem cells. Science 241: 58-62. 18. Kondo, M., I. L. Weissman, and K. Akashi. 1997. Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91: 661-672. 19. Blaho, V. A., S. Galvani, E. Engelbrecht, C. Liu, S. L. Swendeman, M. Kono, R. L. Proia, L. Steinman, M. H. Han, and T. Hla. 2015. HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation. Nature 523: 342-346. 20. Akashi, K., D. Traver, T. Miyamoto, and I. L. Weissman. 2000. A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 404: 193-197. 21. Cohen, S. B., N. L. Smith, C. McDougal, M. Pepper, S. Shah, G. S. Yap, H. Acha-Orbea, A. Jiang, B. E. Clausen, B. D. Rudd, and E. Y. Denkers. 2014. β-catenin signaling drives differentiation and proinflammatory function of IRF8-dependent dendritic cells. The Journal of Immunology. 22. Satpathy, A. T., W. KC, J. C. Albring, B. T. Edelson, N. M. Kretzer, D. Bhattacharya, T. L. Murphy, and K. M. Murphy. 2012. Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages. The Journal of Experimental Medicine 209: 1135-1152. 23. D'Amico, A., and L. Wu. 2003. The early progenitors of mouse dendritic cells and plasmacytoid predendritic cells are within the bone marrow hemopoietic precursors expressing Flt3. The Journal of Experimental Medicine 198: 293-303. 24. Karsunky, H., M. Merad, A. Cozzio, I. L. Weissman, and M. G. Manz. 2003. Flt3 Ligand regulates dendritic cell development from Flt3+ lymphoid and myeloid-committed progenitors to Flt3+ dendritic cells in vivo. The Journal of Experimental Medicine 198: 305-313. 25. Onai, N., A. Obata-Onai, M. A. Schmid, T. Ohteki, D. Jarrossay, and M. G. Manz. 2007. Identification of clonogenic common Flt3+M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow. Nat Immunol 8: 1207-1216. 26. Manz, M. G., D. Traver, T. Miyamoto, I. L. Weissman, and K. Akashi. 2001. Dendritic cell potentials of early lymphoid and myeloid progenitors. Blood 97: 3333-3341. 27. Takizawa, H., S. Boettcher, and M. G. Manz. 2012. Demand-adapted regulation of early hematopoiesis in infection and inflammation. Blood 119: 2991-3002. 28. MacNamara, K. C., K. Oduro, O. Martin, D. D. Jones, M. McLaughlin, K. Choi, D. L. Borjesson, and G. M. Winslow. 2011. Infection-Induced Myelopoiesis during Intracellular Bacterial Infection Is Critically Dependent upon IFN-γ Signaling. The Journal of Immunology 186: 1032-1043. 29. Takizawa, H., R. R. Regoes, C. S. Boddupalli, S. Bonhoeffer, and M. G. Manz. 2011. Dynamic variation in cycling of hematopoietic stem cells in steady state and inflammation. The Journal of Experimental Medicine 208: 273-284. 30. Cain, D. W., P. B. Snowden, G. D. Sempowski, and G. Kelsoe. 2011. Inflammation triggers emergency granulopoiesis through a density-dependent feedback mechanism. PLoS ONE 6: e19957. 31. Massberg, S., P. Schaerli, I. Knezevic-Maramica, M. Köllnberger, N. Tubo, E. A. Moseman, I. V. Huff, T. Junt, A. J. Wagers, I. B. Mazo, and U. H. von Andrian. 2007. Immunosurveillance by hematopoietic progenitor cells trafficking through blood, lymph, and peripheral tissues. Cell 131: 994-1008. 32. Kim, M.-H., J. L. Granick, C. Kwok, N. J. Walker, D. L. Borjesson, F.-R. E. Curry, L. S. Miller, and S. I. Simon. 2011. Neutrophil survival and c-kit+-progenitor proliferation in Staphylococcus aureus–infected skin wounds promote resolution. Blood 117: 3343-3352. 33. Nagai, Y., K. P. Garrett, S. Ohta, U. Bahrun, T. Kouro, S. Akira, K. Takatsu, and P. W. Kincade. 2006. Toll-like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment. Immunity 24: 801-812. 34. Granick, J. L., S. I. Simon, and D. L. Borjesson. 2012. Hematopoietic stem and progenitor cells as effectors in innate immunity. Bone Marrow Research 2012: 8. 35. Hardy, R. R., C. E. Carmack, S. A. Shinton, J. D. Kemp, and K. Hayakawa. 1991. Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow. The Journal of Experimental Medicine 173: 1213-1225. 36. Li, Y.-S., R. Wasserman, K. Hayakawa, and R. R. Hardy. 1996. Identification of the earliest B lineage stage in mouse bone marrow. Immunity 5: 527-535. 37. Allman, D., J. Li, and R. R. Hardy. 1999. Commitment to the B lymphoid lineage occurs before DH-JH recombination. The Journal of Experimental Medicine 189: 735-740. 38. Loffert, D., S. Schaal, A. Ehlich, R. R. Hardy, Y.-R. Zou, W. Müller, and K. Rajewsky. 1994. Early B-cell development in the mouse: insights from mutations introduced by gene targeting. Immunological Reviews 137: 135-153. 39. Osmond, D. G. 1993. The turnover of B-cell populations. Immunology Today 14: 34-37. 40. Chung, J. B., M. Silverman, and J. G. Monroe. 2003. Transitional B cells: step by step towards immune competence. Trends in Immunology 24: 342-348. 41. Osmond, D. G. 1986. Population dynamics of bone marrow B lymphocytes. Immunological Reviews 93: 103-124. 42. Pillai, S., and A. Cariappa. 2009. The follicular versus marginal zone B lymphocyte cell fate decision. Nat Rev Immunol 9: 767-777. 43. Allman, D., and S. Pillai. 2008. Peripheral B cell subsets. Current Opinion in Immunology 20: 149-157. 44. Martin, F., A. M. Oliver, and J. F. Kearney. 2001. Marginal zone and B1 B cells unite in the early response against T-independent blood-borne particulate antigens. Immunity 14: 617-629. 45. Oliver, A. M., F. Martin, G. L. Gartland, R. H. Carter, and J. F. Kearney. 1997. Marginal zone B cells exhibit unique activation, proliferative and immunoglobulin secretory responses. European Journal of Immunology 27: 2366-2374. 46. Oliver, A. M., F. Martin, and J. F. Kearney. 1999. IgMhighCD21high lymphocytes enriched in the splenic marginal zone generate effector cells more rapidly than the bulk of follicular B cells. The Journal of Immunology 162: 7198-7207. 47. Attanavanich, K., and J. F. Kearney. 2004. Marginal zone, but not follicular B cells, are potent activators of naive CD4 T cells. The Journal of Immunology 172: 803-811. 48. Martin, F., and J. F. Kearney. 2002. Marginal-zone B cells. Nat Rev Immunol 2: 323-335. 49. Belperron, A. A., C. M. Dailey, C. J. Booth, and L. K. Bockenstedt. 2007. Marginal zone B-cell depletion impairs murine host defense against Borrelia burgdorferi infection. Infection and Immunity 75: 3354-3360. 50. Tanigaki, K., H. Han, N. Yamamoto, K. Tashiro, M. Ikegawa, K. Kuroda, A. Suzuki, T. Nakano, and T. Honjo. 2002. Notch-RBP-J signaling is involved in cell fate determination of marginal zone B cells. Nat Immunol 3: 443-450. 51. Song, H., and J. Cerny. 2003. Functional heterogeneity of marginal zone B cells revealed by their ability to generate both early antibody-forming cells and germinal centers with hypermutation and memory in response to a T-dependent antigen. The Journal of Experimental Medicine 198: 1923-1935. 52. Cariappa, A., C. Chase, H. Liu, P. Russell, and S. Pillai. 2007. Naive recirculating B cells mature simultaneously in the spleen and bone marrow. Blood 109: 2339-2345. 53. Vinuesa, C. G., S. G. Tangye, B. Moser, and C. R. Mackay. 2005. Follicular B helper T cells in antibody responses and autoimmunity. Nat Rev Immunol 5: 853-865. 54. Zuniga-Pflucker, J. C. 2004. T-cell development made simple. Nat Rev Immunol 4: 67-72. 55. Germain, R. N. 2002. T-cell development and the CD4-CD8 lineage decision. Nat Rev Immunol 2: 309-322. 56. Koch, U., and F. Radtke. 2011. Mechanisms of T cell development and transformation. Annual Review of Cell and Developmental Biology 27: 539-562. 57. Peters, P. J., J. Borst, V. Oorschot, M. Fukuda, O. Krähenbühl, J. Tschopp, J. W. Slot, and H. J. Geuze. 1991. Cytotoxic T lymphocyte granules are secretory lysosomes, containing both perforin and granzymes. The Journal of Experimental Medicine 173: 1099-1109. 58. Lowin, B., M. Hahne, C. Mattmann, and J. Tschopp. 1994. Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways. Nature 370: 650-652. 59. Maher, J., and E. T. Davies. 2004. Targeting cytotoxic T lymphocytes for cancer immunotherapy. British Journal of Cancer 91: 817-821. 60. Carbone, F. R., and M. J. Bevan. 1990. Class I-restricted processing and presentation of exogenous cell-associated antigen in vivo. The Journal of Experimental Medicine 171: 377-387. 61. Jung, S., D. Unutmaz, P. Wong, G.-I. Sano, K. De los Santos, T. Sparwasser, S. Wu, S. Vuthoori, K. Ko, F. Zavala, E. G. Pamer, D. R. Littman, and R. A. Lang. 2002. In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens. Immunity 17: 211-220. 62. Beauvillain, C., Y. Delneste, M. Scotet, A. Peres, H. Gascan, P. Guermonprez, V. Barnaba, and P. Jeannin. 2007. Neutrophils efficiently cross-prime naive T cells in vivo. Blood 110: 2965-2973. 63. Yang, C.-W., B. S. I. Strong, M. J. Miller, and E. R. Unanue. 2010. Neutrophils influence the level of antigen presentation during the immune response to protein antigens in adjuvants. The Journal of Immunology 185: 2927-2934. 64. and, R. R. H., and K. Hayakawa. 2001. B cell development pathways. Annual Review of Immunology 19: 595-621. 65. Nagasawa, T. 2006. Microenvironmental niches in the bone marrow required for B-cell development. Nat Rev Immunol 6: 107-116. 66. Shapiro-Shelef, M., and K. Calame. 2005. Regulation of plasma-cell development. Nat Rev Immunol 5: 230-242. 67. Castillo-Méndez, S. I., C. A. Zago, L. R. Sardinha, A. P. Freitas do Rosário, J. M. Álvarez, and M. R. D’Império Lima. 2007. Characterization of the spleen B-cell compartment at the early and late blood-stage Plasmodium chabaudi Malaria. Scandinavian Journal of Immunology 66: 309-319. 68. Ingold, K., A. Zumsteg, A. Tardivel, B. Huard, Q.-G. Steiner, T. G. Cachero, F. Qiang, L. Gorelik, S. L. Kalled, H. Acha-Orbea, P. D. Rennert, J. Tschopp, and P. Schneider. 2005. Identification of proteoglycans as the APRIL-specific binding partners. The Journal of Experimental Medicine 201: 1375-1383. 69. Baldridge, M. T., K. Y. King, and M. A. Goodell. 2011. Inflammatory signals regulate hematopoietic stem cells. Trends in Immunology 32: 57-65. 70. Whang, M. I., N. Guerra, and D. H. Raulet. 2009. Costimulation of dendritic epidermal γδ T cells by a new NKG2D ligand expressed specifically in the skin. Journal of immunology (Baltimore, Md. : 1950) 182: 4557-4564. 71. Hickey, M. J. 2012. Has Ly6G finally found a job? Blood 120: 1352-1353. 72. Fleming, T. J., M. L. Fleming, and T. R. Malek. 1993. Selective expression of Ly-6G on myeloid lineage cells in mouse bone marrow. RB6-8C5 mAb to granulocyte-differentiation antigen (Gr-1) detects members of the Ly-6 family. The Journal of Immunology 151: 2399-2408. 73. Daley, J. M., A. A. Thomay, M. D. Connolly, J. S. Reichner, and J. E. Albina. 2008. Use of Ly6G-specific monoclonal antibody to deplete neutrophils in mice. Journal of Leukocyte Biology 83: 64-70. 74. Rose, S., A. Misharin, and H. Perlman. 2012. A novel Ly6C/Ly6G-based strategy to analyze the mouse splenic myeloid compartment. Cytometry. Part A : the journal of the International Society for Analytical Cytology 81: 343-350. 75. Boxio, R., C. Bossenmeyer-Pourié, N. Steinckwich, C. Dournon, and O. Nüße. 2004. Mouse bone marrow contains large numbers of functionally competent neutrophils. Journal of Leukocyte Biology 75: 604-611. 76. Lee, C.-k., K. Kim, L. A. Welniak, W. J. Murphy, K. Muegge, and S. K. Durum. 2001. Thymic emigrants isolated by a new method possess unique phenotypic and functional properties. Blood 97: 1360-1369. 77. Webster, N. L., C. Zufferey, J. A. Pane, and B. S. Coulson. 2013. Alteration of the thymic T cell repertoire by rotavirus infection is associated with delayed type 1 diabetes development in non-obese diabetic mice. PLoS ONE 8: e59182. 78. Golde, W. T., P. Gollobin, and L. L. Rodriguez. 2005. A rapid, simple, and humane method for submandibular bleeding of mice using a lancet. Lab Anim (NY) 34: 39-43. 79. Lugaajju, A., S. Reddy, C. Ronnberg, M. Wahlgren, F. Kironde, and K. Persson. 2015. Novel flow cytometry technique for detection of Plasmodium falciparum specific B-cells in humans: increased levels of specific B-cells in ongoing infection. Malaria Journal 14: 370. 80. Song, X.-T., M. E. Turnis, X. Zhou, W. Zhu, B.-X. Hong, L. Rollins, B. Rabinovich, S.-Y. Chen, C. M. Rooney, and S. Gottschalk. 2011. A Th1-inducing adenoviral vaccine for boosting adoptively transferred T cells. Molecular Therapy 19: 211-217. 81. Stehn, J. R., N. K. Haass, T. Bonello, M. Desouza, G. Kottyan, H. Treutlein, J. Zeng, P. R. B. B. Nascimento, V. B. Sequeira, T. L. Butler, M. Allanson, T. Fath, T. A. Hill, A. McCluskey, G. Schevzov, S. J. Palmer, E. C. Hardeman, D. Winlaw, V. E. Reeve, I. Dixon, W. Weninger, T. P. Cripe, and P. W. Gunning. 2013. A novel class of anticancer compounds targets the actin cytoskeleton in tumor cells. Cancer Research 73: 5169-5182. 82. Aichele, P., K. Brduscha-Riem, S. Oehen, B. Odermatt, R. M. Zinkernagel, H. Hengartner, and H. Pircher. 1997. Peptide antigen treatment of naive and virus-immune mice: antigen-specific tolerance versus immunopathology. Immunity 6: 519-529. 83. Durward, M. A., J. Harms, D. M. Magnani, L. Eskra, and G. A. Splitter. 2010. Discordant Brucella melitensis antigens yield cognate CD8(+) T cells in vivo. Infection and Immunity 78: 168-176. 84. Holmes, K. L., L. M. Lantz, and W. Russ. 2001. Conjugation of fluorochromes to monoclonal antibodies. In Current Protocols in Cytometry. John Wiley & Sons, Inc. 85. Lyons, A. B., and C. R. Parish. 1994. Determination of lymphocyte division by flow cytometry. Journal of Immunological Methods 171: 131-137. 86. Thavasu, P. W., S. Longhurst, S. P. Joel, M. L. Slevin, and F. R. Balkwill. 1992. Measuring cytokine levels in blood: importance of anticoagulants, processing, and storage conditions. Journal of Immunological Methods 153: 115-124. 87. Lin, S. L., A. P. Castaño, B. T. Nowlin, M. L. Lupher, and J. S. Duffield. 2009. Bone marrow Ly6Chigh monocytes are selectively recruited to injured kidney and differentiate into functionally distinct populations. The Journal of Immunology 183: 6733-6743. 88. Pillay, J., T. Tak, V. M. Kamp, and L. Koenderman. 2013. Immune suppression by neutrophils and granulocytic myeloid-derived suppressor cells: similarities and differences. Cellular and Molecular Life Sciences 70: 3813-3827. 89. Savina, A., and S. Amigorena. 2007. Phagocytosis and antigen presentation in dendritic cells. Immunological Reviews 219: 143-156. 90. Porgador, A., J. W. Yewdell, Y. Deng, J. R. Bennink, and R. N. Germain. 1997. Localization, quantitation, and in situ detection of specific peptide–MHC class I complexes using a monoclonal antibody. Immunity 6: 715-726. 91. Lipford, G. B., M. Hoffman, H. Wagner, and K. Heeg. 1993. Primary in vivo responses to ovalbumin. Probing the predictive value of the Kb binding motif. The Journal of Immunology 150: 1212-1222. 92. Ueda, Y., M. Kondo, and G. Kelsoe. 2005. Inflammation and the reciprocal production of granulocytes and lymphocytes in bone marrow. The Journal of Experimental Medicine 201: 1771-1780. 93. Nagaoka, H., G. Gonzalez-Aseguinolaza, M. Tsuji, and M. C. Nussenzweig. 2000. Immunization and infection change the number of recombination activating gene (Rag)-expressing B cells in the periphery by altering immature lymphocyte production. The Journal of Experimental Medicine 191: 2113-2120. 94. Ueda, Y., K. Yang, S. J. Foster, M. Kondo, and G. Kelsoe. 2004. Inflammation controls B lymphopoiesis by regulating chemokine CXCL12 expression. The Journal of Experimental Medicine 199: 47-58. 95. Tung, J. W., M. D. Mrazek, Y. Yang, L. A. Herzenberg, and L. A. Herzenberg. 2006. Phenotypically distinct B cell development pathways map to the three B cell lineages in the mouse. Proceedings of the National Academy of Sciences of the United States of America 103: 6293-6298. 96. Zekavat, G., S. Y. Rostami, A. Badkerhanian, R. F. Parsons, B. Koeberlein, M. Yu, C. D. Ward, T.-S. Migone, L. Yu, G. S. Eisenbarth, M. P. Cancro, A. Naji, and H. Noorchashm. 2008. In vivo BLyS/BAFF neutralization ameliorates islet-directed autoimmunity in nonobese diabetic mice. The Journal of Immunology 181: 8133-8144. 97. Laszlo, G., K. S. Hathcock, H. B. Dickler, and R. J. Hodes. 1993. Characterization of a novel cell-surface molecule expressed on subpopulations of activated T and B cells. The Journal of Immunology 150: 5252-5262. 98. Sanderson, R. D., P. Lalor, and M. Bernfield. 1989. B lymphocytes express and lose syndecan at specific stages of differentiation. Cell Regulation 1: 27-35. 99. Nutt, S. L., P. D. Hodgkin, D. M. Tarlinton, and L. M. Corcoran. 2015. The generation of antibody-secreting plasma cells. Nat Rev Immunol 15: 160-171. 100. Godfrey, D. I., J. Kennedy, T. Suda, and A. Zlotnik. 1993. A developmental pathway involving four phenotypically and functionally distinct subsets of CD3-CD4-CD8- triple-negative adult mouse thymocytes defined by CD44 and CD25 expression. The Journal of Immunology 150: 4244-4252. 101. Klein, L., B. Kyewski, P. M. Allen, and K. A. Hogquist. 2014. Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see). Nat Rev Immunol 14: 377-391. 102. Starr, T. K., S. C. Jameson, and K. A. Hogquist. 2003. Positive and negative selection of T cells. Annual Review of Immunology 21: 139-176. 103. Azzam, H. S., A. Grinberg, K. Lui, H. Shen, E. W. Shores, and P. E. Love. 1998. CD5 expression is developmentally regulated by T cell receptor (TCR) signals and TCR avidity. The Journal of Experimental Medicine 188: 2301-2311. 104. Aliahmad, P., and J. Kaye. 2008. Development of all CD4 T lineages requires nuclear factor TOX. The Journal of Experimental Medicine 205: 245-256. 105. Schuettpelz, L. G., and D. C. Link. 2013. Regulation of hematopoietic stem cell activity by inflammation. Frontiers in Immunology 4: 204. 106. Zhao, X., G. Ren, L. Liang, P. Z. Ai, B. Zheng, J. A. Tischfield, Y. Shi, and C. Shao. 2010. Brief report: interferon-γ induces expansion of Lin−Sca-1+C-Kit+ cells. STEM CELLS 28: 122-126. 107. Holmes, C., and W. L. Stanford. 2007. Concise review: stem cell antigen-1: expression, function, and enigma. STEM CELLS 25: 1339-1347. 108. Trumpp, A., M. Essers, and A. Wilson. 2010. Awakening dormant haematopoietic stem cells. Nat Rev Immunol 10: 201-209. 109. Eyles, J. L., M. J. Hickey, M. U. Norman, B. A. Croker, A. W. Roberts, S. F. Drake, W. G. James, D. Metcalf, I. K. Campbell, and I. P. Wicks. 2008. A key role for G-CSF–induced neutrophil production and trafficking during inflammatory arthritis. Blood 112: 5193-5201. 110. Semerad, C. L., F. Liu, A. D. Gregory, K. Stumpf, and D. C. Link. 2002. G-CSF is an essential regulator of neutrophil trafficking from the bone marrow to the blood. Immunity 17: 413-423. 111. Ostrand-Rosenberg, S. 2004. Animal models of tumor immunity, immunotherapy and cancer vaccines. Current Opinion in Immunology 16: 143-150. 112. Manz, M. G., and S. Boettcher. 2014. Emergency granulopoiesis. Nat Rev Immunol 14: 302-314. 113. Delano, M. J., K. M. Kelly-Scumpia, T. C. Thayer, R. D. Winfield, P. O. Scumpia, A. G. Cuenca, P. B. Harrington, K. A. O’Malley, E. Warner, S. Gabrilovich, C. E. Mathews, D. Laface, P. G. Heyworth, R. Ramphal, R. M. Strieter, L. L. Moldawer, and P. A. Efron. 2011. Neutrophil mobilization from the bone marrow during polymicrobial sepsis is dependent on CXCL12 signaling. The Journal of Immunology 187: 911-918. 114. Maletto, B. A., A. S. Ropolo, D. O. Alignani, M. V. Liscovsky, R. P. Ranocchia, V. G. Moron, and M. C. Pistoresi-Palencia. 2006. Presence of neutrophil-bearing antigen in lymphoid organs of immune mice. Blood 108: 3094-3102. 115. Calabro, S., M. Tortoli, B. C. Baudner, A. Pacitto, M. Cortese, D. T. O’Hagan, E. De Gregorio, A. Seubert, and A. Wack. 2011. Vaccine adjuvants alum and MF59 induce rapid recruitment of neutrophils and monocytes that participate in antigen transport to draining lymph nodes. Vaccine 29: 1812-1823. 116. Morel, S., A. Didierlaurent, P. Bourguignon, S. Delhaye, B. Baras, V. Jacob, C. Planty, A. Elouahabi, P. Harvengt, H. Carlsen, A. Kielland, P. Chomez, N. Garçon, and M. Van Mechelen. 2011. Adjuvant System AS03 containing α-tocopherol modulates innate immune response and leads to improved adaptive immunity. Vaccine 29: 2461-2473. 117. Yang, C.-W., and E. R. Unanue. 2013. Neutrophils control the magnitude and spread of the immune response in a thromboxane A(2)-mediated process. The Journal of Experimental Medicine 210: 375-387. 118. Bratton, D. L., and P. M. Henson. 2011. Neutrophil clearance: when the party is over, clean-up begins. Trends in Immunology 32: 350-357. 119. Ebaid, H. 2014. Neutrophil depletion in the early inflammatory phase delayed cutaneous wound healing in older rats: improvements due to the use of un-denatured camel whey protein. Diagnostic Pathology 9: 46. 120. Joffre, O. P., E. Segura, A. Savina, and S. Amigorena. 2012. Cross-presentation by dendritic cells. Nat Rev Immunol 12: 557-569. 121. Gruver, A. L., and G. D. Sempowski. 2008. Cytokines, leptin, and stress-induced thymic atrophy. Journal of Leukocyte Biology 84: 915-923. 122. Billard, M. J., A. L. Gruver, and G. D. Sempowski. 2011. Acute Endotoxin-Induced Thymic Atrophy Is Characterized By Intrathymic Inflammatory and Wound Healing Responses. PLoS ONE 6: e17940. 123. de Meis, J., D. Aurélio Farias-de-Oliveira, P. H. Nunes Panzenhagen, N. Maran, D. M. S. Villa-Verde, A. Morrot, and W. Savino. 2012. Thymus atrophy and double-positive escape are common features in infectious diseases. Journal of Parasitology Research 2012: 9. 124. Yang, Y.-W., C.-A. Wu, and W. J. W. Morrow. 2004. Cell death induced by vaccine adjuvants containing surfactants. Vaccine 22: 1524-1536. 125. Shi, Y., W. Zheng, and K. L. Rock. 2000. Cell injury releases endogenous adjuvants that stimulate cytotoxic T cell responses. Proceedings of the National Academy of Sciences 97: 14590-14595. 126. Albert, M. L., B. Sauter, and N. Bhardwaj. 1998. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392: 86-89. 127. Sauter, B., M. L. Albert, L. Francisco, M. Larsson, S. Somersan, and N. Bhardwaj. 2000. Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. The Journal of Experimental Medicine 191: 423-434. 128. Coffman, R. L., A. Sher, and R. A. Seder. 2010. Vaccine adjuvants: Putting innate immunity to work. Immunity 33: 492-503. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/3991 | - |
dc.description.abstract | L121-adjuvant (L121-adj.)為一含有Pluronic L121 block copolymer、Tween 80與squalane等成分之疫苗佐劑。本論文研究目的為探討此L121-adj.所引發之免疫反應,包含毒殺T細胞(cytotoxicity T lymphocyte, CTL)反應、對抗腫瘤增生,與其所造成之發炎反應對於顆粒性白血球、B細胞、T細胞、血液幹細胞、前驅細胞[hematopoietic stem/progenitor cell (HSPC)]等免疫細胞分化的影響。
在第一部分的研究中,我們證實皮下注射L121-adj.與抗原能夠有效產生抗原專一性CTL反應,與可以做為治療性疫苗,抑制B16F10黑色素細胞腫瘤的增生。為了瞭解L121-adj.產生CTL的機制,我們以流式細胞儀分析了不同組織中的抗原呈現細胞,發現注射L121-adj.會導致局部注射皮下位置產生發炎反應,吸引顆粒性白血球與樹突細胞至注射部位,並且促進顆粒性白血球與樹突細胞吞噬攜帶抗原至淋巴結中,同時導致骨髓中的顆粒性白血球釋放減少,增加脾臟中的顆粒性白血球。除此之外,我們發現注射位置中的樹突細胞能夠透過MHC-I呈現抗原,使CD8+ T細胞活化。為了瞭解顆粒性白血球是否能夠活化CD8+ T細胞,我們以抗體去除體內顆粒性白血球後,然而卻不會降低L121-adj.所產生的CTL反應。以上實驗結果證明注射部位中的抗原呈現細胞是活化CTL之重要機制。 第二部分的研究裡,為了分析L121-adj.對於T細胞與B細胞發育分化的影響,我們以流式細胞儀分析骨髓與脾臟中的B細胞,與胸腺中的T細胞的CD marker表現型。我們發現注射L121-adj.之後的發炎反應會驅使骨髓中的前驅B細胞減少,並轉移至脾臟中分化為transitional B細胞,以產生更多的marginal zone B細胞以及follicular B細胞,進一步使脾臟中產生germinal center B細胞與plasma B細胞。L121-adj.亦加速胸腺中T細胞之發育成熟,使更高比例的前驅T細胞通過positive selection,成熟為CD4+ T細胞。 第三部分的研究中,為了分析L121-adj.對於HSPCs分化的影響,我們以流式細胞儀分析骨髓中的HSPCs,我們發現注射L121-adj.後會改變血液系統的恆定狀態(homeostasis),造成血液幹細胞分化為更多顆粒性白血球與巨噬細胞,並且減少common lymphoid progenitors (CLPs)之分化。表示L121-adj.所造成之發炎反應能夠調控血液幹細胞的分化。 綜合以上結果,證明注射L121-adj.會造成多層次的影響,包含增加樹突細胞的抗原呈現能力,並且活化毒殺T細胞,抑制腫瘤增生。與促進T細胞、B細胞的分化成熟。另一方面,透過血液調控骨髓中血液幹細胞分化,以產生更多的顆粒性白血球,補償顆粒性白血球的消耗。 | zh_TW |
dc.description.abstract | The objective of this study was to examine the immunological effect induced by the L121-adjvant (L121-adj.), an emulsion vaccine adjuvant consisting of Pluronic L121, Tween 80, and squalane, including the cytotoxicity T lymphocyte (CTL) response and the differentiation of B cells, T cells, and the hematopoietic stem/progenitor cells (HSPCs).
Vaccination of B16F10 melanoma-bearing mice with L121-adj. containing ovalbumin (OVA) induced an antigen-specific CTL response, resulted in an inhibition of tumor growth with an increased the survival rate. Flow cytometric analysis illustrated both dendritic cells and granulocytes were recruited to the injection sites after vaccination, and antigens were transported to draining lymph nodes by the antigen presenting cells (APCs). Accelerated production of granulocytes was observed in the bone marrow, in response to inflammation induced by vaccination, followed by moving into the spleen. Dendritic cells were able to effectively cross-present antigen in vivo via MHC-I molecule and activate the CD8+ T cells. Depletion of granulocytes prior to immunization resulted in an enhanced CTL response. Injection of L121-adj. promoted the translocation of B cell precursors from bone marrow to the spleen, resulted in the differentiation of transitional B cells into marginal zone B cells and follicular B cells, followed by the formation of germinal center and plasma B cells. Positive selection of developing T cells in the thymus was accelerated by the treatment of L121-adj., resulted in a significant production of mature CD4+ T cells. Modification of hematopoietic homeostasis was also noticed after vaccination of animals with L121-adj. Flow cytometric analysis showed marked increase of Lin-Sca-1+c-Kit+ (LSK) hematopoietic stem cells (HSCs) and consequently the granulocyte-macrophage progenitors (GMPs), presumably at an expense of the common myeloid progenitors (CMPs). Generation of F4/80+ and Ly6G+ cells from LSK, CMPs, and GMPs was profoundly increased due to the presence of granulocyte colony-stimulating factor (G-CSF) in the serum of immunized mice. Taken together, injection of mice with L121-adj. exhibited several immunological effects, including the recruitment of dendric cells for the activation of CTL, promoting the differentiation and maturation of progenitors of B and T progenitors into functional lymphocytes. L121-adj. also triggers the differentiation and proliferation of hematopoietic stem/progenitor cells (HSPCs), giving rise to the generation of granulocytes in the bone marrow of immunized animals. | en |
dc.description.provenance | Made available in DSpace on 2021-05-13T08:39:58Z (GMT). No. of bitstreams: 1 ntu-105-R01423032-1.pdf: 6663010 bytes, checksum: f0821ed6c53676967b820be0d7affd8a (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 中文摘要 i
Abstract iii 第一章 文獻回顧 1 1.1 疫苗佐劑(vaccine adjuvant)之概要 1 1.2 含有Pluronic L121 block co-polymer之疫苗佐劑介紹 1 1.3 血液幹細胞及前驅細胞(hematopietic stem/progenitor cells, HSPCs)的分化 2 1.4 發炎反應影響血液幹細胞及前驅細胞的分化 3 1.5 B細胞的發育及分化 3 1.6 胸腺中T細胞的發育及分化 4 1.7 毒殺T細胞(CTL)與MHC-I cross presentation 4 第二章 研究目的與實驗設計 9 第三章 材料與方法 12 3.1 藥品試劑 (依照字母排序) 12 3.2 培養基與緩衝液配方 13 3.3 用於流式細胞儀分析之螢光抗體與純化CD8+細胞所用的抗體 13 3.4 用於免疫螢光染色所使用之抗體 15 3.5 小鼠品系 15 3.6 疫苗佐劑與注射方式 15 3.7 流式細胞儀與小鼠組織細胞的處理方式 16 3.8 腫瘤的植入與測量 17 3.9 體內專一性殺手型T細胞(Cytotoxicity T Lymphocytes, CTL)的細胞毒殺能力試驗 17 3.10 分析L121-adj.對於骨髓內髓細胞(myeloid cells)以及脾臟與淋巴結中顆粒性白血球、樹突細胞分化的影響 18 3.11 在OVA上標記FITC的方法 18 3.12 分析L121-adj.對於淋巴結中顆粒性白血球與樹突細胞吞噬抗原能力的影響 19 3.13 分析L121-adj.對於局部皮下注射部位中顆粒性白血球與樹突細胞抗原呈現的影響 19 3.14 測試局部皮下注射部位中顆粒性白血球與樹突細胞的交叉呈現能力 19 3.15 體內去除顆粒性白血球後測量專一性細胞毒殺T細胞活性 20 3.16 分析L121-adj.對骨髓、脾臟中B細胞與胸腺T細胞分化的影響 21 3.17 骨髓腔內注射前驅B細胞後分析L121-adj.對於前驅B細胞的分化的影響 22 3.18 分析L121-adj.對骨髓中血液幹細胞分化的影響 22 3.19 分析L121-adj.對於CLP細胞分化能力的影響 22 3.20 以ELISA測量注射L121-adj.後小鼠血液中G-CSF濃度 23 3.21 以小鼠血清體外培養LSK、CMP、GMP細胞與分析其分化 24 3.22 皮下注射部位切片組織免疫螢光染色以及細胞型態之顯微鏡觀察 24 4.1 注射含L121-adj.與抗原OVA 之疫苗能夠抑制B16F10-OVA黑色素細胞瘤之生長,與延長小鼠存活時間 26 4.2 注射含L121-adj.與抗原OVA 之疫苗能夠於一周之內產生抗原專一性之T細胞毒殺免疫反應(CTL) 26 4.3 注射L121-adj.促使顆粒性白血球與單核細胞離開骨髓 28 4.4 注射L121-adj.促使脾臟中顆粒性白血球增加,並且表現出F4/80表面抗原 29 4.5 注射L121-adj.增加顆粒性白血球與樹突細胞的輸送抗原至淋巴結中 30 4.6 注射L121-adj.吸引顆粒性白血球與樹突細胞浸潤局部注射位置,並且使樹突細胞獲得抗原呈現的能力 31 4.7 以1A8單株抗體能夠有效減少體內顆粒性白血球的數量,在施打疫苗前去除體內顆粒性白血球能夠增加毒殺性T細胞的活性 33 4.8 注射L121-adj.影響骨髓內B細胞的分化,減少骨髓內前驅B細胞的數量 35 4.9 注射L121-adj.促進脾臟中B細胞的分化,使marginal zone B細胞的數量增加,並且產生germinal center B細胞與plasma B細胞。 37 4.10 注射L121-adj.促使骨髓中前驅B細胞轉移到脾臟中分化成transitional B細胞 39 4.11注射L121-adj.影響胸腺T細胞的分化,並且使胸腺T細胞減少 39 4.12 注射L121.adj.促進胸腺中T細胞之成熟,加速正向選擇(positive selection) 41 4.13 注射L121-adj.影響骨髓中血液幹細胞的分化,改變血液幹細胞的恆定性 43 4.14 注射L121-adj.使骨髓中CLP細胞之Sca-1表現短暫提高 45 4.15 注射L121-adj.抑制CLP細胞的分化,減少B細胞的產生 46 4.16 注射L121-adj.使血液中G-CSF濃度大量提昇 46 4.17 L121-adj.透過血液中的細胞激素影響骨髓中血液幹細胞產生大量顆粒性白血球 47 第五章 討論 49 第六章 結論 55 參考文獻 57 圖表目錄 示意圖 一、簡化之血液幹細胞分化階層模型圖(hierarchy model) 6 示意圖 二、簡化之B細胞分化理論模型圖 7 示意圖 三、簡化之T細胞分化理論模型圖 8 圖 一、 注射L121-adj.以及OVA抗原能有效抑制B16F10-OVA黑色素細胞腫瘤的增生以及增加動物存活率 68 圖 二、 注射L121-adj.以及OVA抗原能有效在六天之內產生抗原專一性之細胞毒殺反應 70 圖 三、 注射L121-adj.影響骨髓中顆粒性白血球與單核細胞的發育 72 圖 四、 注射L121-adj.使脾臟中顆粒性白血球增加,並且使顆粒性白血球表現出F4/80表面抗原 77 圖 五、 注射L121-adj.使淋巴結中顆粒性白血球表現出F4/80表面抗原 79 圖 六、 注射L121-adj.增加樹突細胞以及顆粒細胞輸送抗原至淋巴結中 81 圖 七、 注射L121-adj.使該局部注射位置吸引更多的樹突細胞以及顆粒性白血球浸潤,並且使樹突細胞表現出MHC-I-SIINFEKL抗原呈現機制 83 圖 八、 注射L121-adj.使該局部注射位置發炎腫脹,並且吸引樹突細胞以及顆粒性白血球至組織中 86 圖 九、 注射L121-adj.使樹突細胞獲得抗原呈現的能力 89 圖 十、 In vivo去除顆粒性白血球後,再注射L121-adj.使專一性毒殺性T細胞毒殺能力增加 91 圖 十一、 注射L121-adj.影響骨髓中B細胞的發育,並且減少骨髓中B細胞之數量 94 圖 十二、 注射L121-adj.影響脾臟中B細胞的分化,增加germinal center B細胞以及plasma B細胞 99 圖 十三、 注射L121-adj.使骨髓中前驅B細胞轉移到脾臟中,成為transitional B細胞 104 圖 十四、 注射L121-adj.影響胸線中T細胞的發育,並且減少T細胞的數量 106 圖 十五、 注射L121-adj.影響胸線中T細胞的發育,加速T細胞的成熟 111 圖 十六、 注射L121-adj.影響骨髓中血液幹細胞以及免疫細胞的分化 114 圖 十七、 注射L121-adj.使骨髓中CLP細胞表現高量Sca-1表面抗原 119 圖 十八、注射L121-adj.抑制CLP細胞分化,減少B細胞產生 121 圖 十九、注射L121-adj.在血液中產生立即性的G-CSF濃度提升 124 圖 二十、注射L121-adj.後小鼠血液中可使血液細胞分化成顆粒性白血球以及巨噬細胞 126 附錄圖 一、注射L121-adj.後使脾臟中CD8+ T細胞產生IFN-γ以及granzyme B 129 附錄圖 二、C57BL/6小鼠骨髓中的CD11b+Gr-1intLy6Cint細胞的外觀型態以及經過體外培養成熟後可發育成顆粒性白血球 130 附錄圖 三、注射L121-adj.後,C57BL/6小鼠骨髓中CD11b+Gr-1‒細胞以及CD11b+Gr-1intLy6C‒細胞數量隨時間的變化 131 附錄圖 四、注射L121-adj.後脾臟中Ly6G+CD11b+顆粒性白血球不會抑制CD8+ T細胞的活化增生 133 | |
dc.language.iso | zh-TW | |
dc.title | 疫苗佐劑對於血液細胞分化影響之研究 | zh_TW |
dc.title | Effects of vaccine adjuvant on hematopoiesis | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-1 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 伍安怡,李建國,繆希椿 | |
dc.subject.keyword | 疫苗佐劑,毒殺T細胞,免疫細胞分化, | zh_TW |
dc.subject.keyword | CTL;Development of immune cells,Hematopoiesis,Vaccine adjuvant, | en |
dc.relation.page | 133 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2016-02-04 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 藥學研究所 | zh_TW |
顯示於系所單位: | 藥學系 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-105-1.pdf | 6.51 MB | Adobe PDF | 檢視/開啟 |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。