分泌IL-4潛能為表現Qa-2low週邊naïve CD4+ T細胞微亞群之特徵

Abstract

在週邊組織和胸腺中的NK1-CD4+8-CD44lo T 細胞其表面的Qa-2會隨著年紀增加而有遞增的現象,但在週邊組織中的NK1-CD4+8-CD44lo T細胞所表現出的最高量Qa-2和胸腺中的細胞來做比較時是呈現較低的情況,隨著年紀遞增其Qa-2表現的特性可能在週邊組織中的細胞是比較有較大的應用價值。Qa-2在各個週邊組織中主要只在 NK1-CD4+8-CD44lo T細胞上表現的較高。另一方面，Qa-2在骨髓和胸腺中的NK1-CD4+8-CD44lo T 細胞表面上表現的較低且較不一致。儘管在胸腺中的細胞其第四介白素誘發能力較高，胸腺和脾臟中的NK1-CD4+8-CD44lo T 細胞都被發現具有第四介白素誘發能力 (IL-4 inducibility)和Qa-2表現量是呈現反相關性的特性。相似的結果也在剔除p59fyn或IL-4R基因的小鼠中發現。經由進一步在脾臟中的Qa-2lowNK1-CD4+8-CD44lo T 細胞分離出Vb(2/7/8)＋細胞亞群可以發現有更加強的第四介白素誘發能力。Qa-2lowNK1-CD4+8-CD44lo T 細胞所分泌的第四介白素可以在沒有外加任何細胞激素(cytokine)－的情況下促使本身走向第二型免疫細胞 (TH2 effecter cells )。在第一型免疫反應的誘導(TH1 priming condition)刺激下，脾臟中Qa-2lo 和Qa-2hi 的NK1-CD4+8-CD44lo T細胞亞群都能分化成具大量分泌第三型干擾素(IFN-g)能力的第一型免疫細胞(TH1 effecter cells)，且Qa-2lo細胞亞群的分化能力也比Qa-2hi細胞亞群強。在第二型免疫反應的誘導(TH2 priming condition)下，Qa-2lo 和Qa-2hi 的NK1-CD4+8-CD44lo T細胞亞群都能分化成大量分泌第四介白素的第二型免疫細胞(TH2 effecter cells)，且Qa-2lo細胞亞群也有較高的分化能力。因此，我們可以得知在擁有低量第四介白素誘發能力的naïve CD4+ T 細胞中主要是透過少量擁有高量第四介白素誘發能力的細胞亞群去分泌第四介白素，而非所有或大部分的細胞都擁有低量的第四介白素誘發能力。此外，這個屬於naïve型態、擁有迅速第四介白素誘發能力,且分布在各個週邊組織中的一小群NK1-CD4+8-CD44lo T 細胞亞群被認為可以透過快速分泌第四介白素去引發第二型免疫反應和其他第四介白素所必須的免疫反應。

Both peripheral and thymus NK1-CD4+CD8-CD44low T cells displayed an age-associated increase in Qa-2 expression, but the magnitude of the increase was relatively small for NK1-CD4+CD8-CD44low thymocytes and was much more pronounced for peripheral NK1-CD4+CD8-CD44low T cells. Qa-2 expression was uniformly high for the vast majority of NK1-CD4+CD8-CD44low T cells obtained from peripheral tissues and organs. On the other hand, Qa-2 expression was weaker and more heterogeneous for NK1-CD4+CD8-CD44low T cells from the thymus. An inverse correlation between the level of Qa-2 expression and IL-4 inducibility was found for both thymus and spleen NK1-CD4+CD8-CD44low T cells, although the level of IL-4 inducibility was significantly higher for cells from the thymus than the spleen. Similar enrichment of IL-4 inducibility in peripheral NK1-CD4+CD8-CD44low T cells was observed in mice carrying disrupted p59fyn or il4r genes. Isolation of the Vb(2/7/8)+ subset from spleen Qa-2lowNK1-CD4+CD8-CD44low T cells resulted in further enrichment in IL-4 inducibility. In the absence of exogenously added cytokines, TCR-stimulated IL-4 production by spleen Qa-2lowNK1-CD4+8-CD44low T cells promoted their own differentiation toward Th2 effectors in an IL-4-dependent manner. Under Th1 priming conditions, both Qa-2low and Qa-2hi subsets of spleen NK1-CD4+CD8-CD44low T cells differentiated into high level IFNg-producing Th1 effectors. Under Th2 priming conditions, both Qa-2low and Qa-2hi subsets of spleen NK1-CD4+CD8-CD44low T cells differentiated into high level IL-4-produccing Th2 effectors. Thus, the generally accepted low level IL-4 inducibility by naïve CD4+ T cells is due to high level IL-4 inducibility by a small subpopulation of peripheral CD4+ T cells and not due to low level IL-4 inducibility by all or most naïve CD4+ T cells. Furthermore, this small subset of Qa-2lowNK1-CD4+CD8-CD44low T cells, by virtue of its naïve phenotype, prompt IL-4 inducibility, and distribution in the periphery, is expected to play a significant role in the initial stages of immune response by rapidly releasing IL-4 which may in turn direct Th2 response and other IL-4-dependent processes.