口腔扁平苔癬以及口腔癌病人周邊CD8+ T細胞的分析

Abstract

人類周邊血毒殺性T細胞可以藉由兩個細胞表面的標定CD45RA和CCR7分成四群細胞，分別為原始T細胞、中心記憶性T細胞(TCM)、效應記憶性T細胞(TEM)和終末分化的作用細胞(TEMRA)，在毒殺性作用T細胞中介白素7的受器下游基因的活化和自體免疫性疾病的治療後回復有關，在我們之前的研究中發現表現IFN- γ+granzyme B+的周邊血毒殺性T細胞在口腔癌病人以及口腔扁平苔蘚病人的周邊血中相較於正常人佔有較高的比例，另一方面，病人體內中周邊血毒殺性T細胞表現介白素7受器alpha鍵(CD127)的細胞較正常人明顯的減少。在我的研究中，我想要比較CD127的表現是否會影響毒殺性T細胞亞群的細胞特性，像是細胞激素的釋放或是細胞存活的能力。我們發現口腔癌或是口腔扁平苔蘚病人周邊血中效應記憶性T細胞和終末分化的作用細胞的比例會較正常人要高許多，而且大部分浸潤到口腔癌組織或是口腔扁平苔蘚病部的細胞是效應記憶性T細胞和終末分化的作用細胞這兩群，反轉錄聚合酶鏈反應的結果顯示這兩群細胞表現丙型干擾素(IFN-γ)、顆粒溶解酶B(granzyme B)和穿洞素(perforin)的訊息RNA較原始T細胞或是中心記憶性T細胞高，我們分別測量表現CD127的效應記憶性T細胞和終末分化的作用細胞以及未表現CD127的細胞，發現不論是在訊息RNA或是細胞激素的放出，有表現CD127的細胞群都有較高的丙型干擾素和介白素2的表現，此外，在抗源刺激之後，表現CD127的細胞相較於不表現的細胞會有比較好的細胞增殖和比較少的細胞死亡。總和以上的結果，效應記憶性T細胞和終末分化的作用細胞可能是造成口腔扁平苔蘚病人口腔細胞損傷和口腔癌病人中殺死癌細胞的主要作用細胞群。

Based on the expression of CD45RA and CCR7, human peripheral blood CD8+ T cell is sub-divided into naïve, central memory (TCM), effector memory (TEM) and terminally differentiated effector cells (TEMRA). The expression of IL-7 receptor and cognate downstream signaling molecules in CD8 effector cells was found to be correlated with the prognosis of autoimmune disease. Previously, we found that the frequency of IFN- γ+ granzyme B+ CD8+ T cell in peripheral blood from either oral cancer or oral lichen planus (OLP) patients was significantly higher, while the expression of IL-7 receptor α chain, CD127, in CD8+ T cells was lower than in healthy control. The specific aim of this study is to identify the CD127 expression on distinct CD8+ T cell subsets and characterize their differences in cytokine production and survival after stimulation. The distribution of peripheralCD8+ TEM or TEMRA subsets is significantly increased in cancer and autoimmune patients. Moreover, these CD8+ T cell subpopulations are also found infiltrating into OLP lesion or tumor site. RT-PCR analysis of sorted CD8+T cells from oral cancer or OLP patients indicated that TEM or TEMRA express significantly higher level of mRNAs encoding IFN-γ, granzyme B and perforin than the naïve or central memory counterparts. Interestingly, CD127+ TEM or TEMRA subsets express and produce higher level of IFN-γ and IL-2 than CD127- subsets and exhibits higher proliferating ability and resistance to apoptosis following stimulation. Together, these results suggested that TEM and TEMRA may be the predominant effector cell subsets to cause OLP lesion or anti-tumor immunity.