TGF-β and IL-10 Production by HIV-Specific CD8+T Cells Is Regulated by CTLA-4 Signaling on CD4+T Cells
TGF-β and IL-10 Production by HIV-Specific CD8+T Cells Is Regulated by CTLA-4 Signaling on CD4+T Cells
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DOI：
10.1371/journal.pone.0008194
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发表时间：
2009-12-14
期刊：
影响因子：
3.7
通讯作者：
Cao, Huyen
中科院分区：
文献类型：
--
作者：
Elrefaei, Mohamed;Burke, Candace M.;Cao, Huyen
HIV-1感染中的免疫失调与抑制性分子如CTLA-4、TGF-β和IL-10的表达增加有关。在这项研究中，我们研究了一个潜在的机制，调节TGF-β和IL-10表达的HIV特异性抑制CD 8 + T细胞。没有观察到HIV特异性CD 8 + T细胞产生TGF-β、IL-10和IFN-γ细胞因子之间的重叠。TGF-β阳性和IL-10阳性的细胞是FOXP 3阴性的，CD 25阴性的，并且显示出CD 127的异质性表面表达。TGF-β和IL-10阳性CD 8 + T细胞不表达CTLA-4。然而，CTLA-4阻断导致HIV特异性TGF-β阳性和IL-10阳性CD 8 + T细胞应答显著降低，并且伴随HIV特异性IFN-γ阳性CD 8 + T细胞应答增加。CD 4 + T细胞的消耗消除了CTLA-4对HIV特异性TGF-β阳性和IL-10阳性CD 8 + T细胞的影响。我们的研究表明，CD 4 + T细胞上的CTLA-4信号调节HIV特异性抑制性CD 8 + T细胞的抑制功能。
Immune dysregulation in HIV-1 infection is associated with increased expression of inhibitory molecules such as CTLA-4, TGF-beta, and IL-10. In this study we examined one potential mechanism for regulating TGF-beta and IL-10 expression by HIV-specific suppressor CD8+ T cells. No overlap between TGF-beta, IL-10, and IFN-gamma cytokine production by HIV-specific CD8+ T cells was observed. TGF-beta positive and IL-10 positive cells were FOXP3 negative, CD25 negative, and displayed a heterogeneous surface expression of CD127. TGF-beta and IL-10 positive CD8+ T cells did not express CTLA-4. Nevertheless, CTLA-4 blockade resulted in a significant decrease in HIV-specific TGF-beta positive and IL-10 positive CD8+ T cell responses, and a concomitant increase in HIV-specific IFN-gamma positive CD8+ T cell responses. Depletion of CD4+ T cells abrogated the impact of CTLA-4 on HIV-specific TGF-beta positive and IL-10 positive CD8+ T cells. Our study suggests that CTLA-4 Signaling on CD4+ T cells regulates the inhibitory functions of the HIV-specific suppressor CD8+ T cells.