The capacity of the natural ligands for CD28 to drive IL-4 expression in naive and antigen-primed CD4+ and CD8+ T cells
The capacity of the natural ligands for CD28 to drive IL-4 expression in naive and antigen-primed CD4+ and CD8+ T cells
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DOI：
10.1093/intimm/dxh188
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发表时间：
2005-01-01
影响因子：
4.4
通讯作者：
Fujiwara, H
中科院分区：
文献类型：
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作者：
Bian, Y;Hiraoka, S;Fujiwara, H
B7/CD 28共刺激通路在T细胞活化包括Th 1/Th 2分化中起关键作用。然而，关于CD 28共刺激是否有利于Th 1和Th 2或两者的极化知之甚少。在这里，我们显示了CD 28分子（B7.2-IG或B7.1-IG融合蛋白）的天然配体的关键作用，特别是在诱导2型T细胞极化。在用次优剂量的抗CD 3进行TCR触发后，用抗CD 28 mAb或B7-IG融合蛋白共刺激初始CD 4（+）T细胞导致相当水平的IFN-γ产生。当CD 28与B7-IG共刺激时，幼稚T细胞可以产生IL-4，而与抗CD 28共刺激时则不能。当在B7-IG存在下用OVA刺激来自抗OVATCR转基因小鼠的T细胞时，也观察到IL-4选择性上调。与IL-4表达相关，B7-IG共刺激比抗CD 28 mAb更有效地诱导加塔-3表达，而这两种共刺激试剂对T-bet的诱导相当。这种B7效应也适用于幼稚和抗原致敏的CD 8（+）T细胞：在B7-IG共刺激的情况下，分别用抗CD 3和回忆抗原刺激幼稚和同种抗原致敏的T细胞时，产生表达IL-4的CD 8（+）T细胞。重要的是，这种CD 8（+）T细胞分化需要在初始TCR刺激期间CD 4（+）T细胞的共存。这些观察结果表明，虽然CD 8（+）T细胞的分化依赖于CD 4（+）细胞，但通过CD 28与其天然配体的共刺激有效诱导2型CD 4和CD 8 T细胞极化。
The B7/CD28 costimulatory pathway plays a critical role in T cell activation including Th1/Th2 differentiation. However, little is known about whether CD28 costimulation favors polarization of either Th1 and Th2 or both. Here, we show a critical role of the natural ligands for CD28 molecules (B7.2-Ig or B7.1-Ig fusion proteins), particularly in the induction of type 2 T cell polarization. Upon TCR-triggering with suboptimal doses of anti-CD3, costimulation of naive CD4(+) T cells with anti-CD28 mAb or B7-Ig fusion proteins led to comparable levels of IFN-gamma production. Naive T cells could produce IL-4 when CD28 costimulation was done with B7-Ig, but not with anti-CD28. IL-4-selective upregulation was also observed when T cells from anti-OVA TCR transgenic mice were stimulated with OVA in the presence of B7-Ig. Correlating with IL-4 expression, GATA-3 expression was induced much more potently by costimulation with B7-Ig than with anti-CD28 mAb, while T-bet induction by these two costimulatory reagents was comparable. This B7 effect was also applied for naive and antigen-primed CD8(+) T cells: IL-4-expressing CD8(+) T cells were generated when naive and alloantigen-primed T cells were stimulated with anti-CD3 and recall antigens, respectively, in the presence of B7-Ig costimulation. Importantly, such CD8(+) T cell differentiation required the coexistence of CD4(+) T cells during the initial TCR stimulation. These observations indicate that both type 2 CD4 and CD8 T cell polarizations are efficiently induced via costimulation of CD28 with its natural ligands, although the differentiation of CD8(+) T cells is dependent on CD4(+) cells.