Cytokines and cell surface molecules independently induce CXCR4 expression on CD4+ CCR7+ human memory T cells
Cytokines and cell surface molecules independently induce CXCR4 expression on CD4+ CCR7+ human memory T cells
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DOI：
10.4049/jimmunol.165.2.716
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发表时间：
2000-07-15
影响因子：
4.4
通讯作者：
Yssel, H
中科院分区：
文献类型：
--
作者：
Jourdan, P;Vendrell, JP;Yssel, H
在本研究中，我们发现IL-2、IL-4、IL-7和IL-15能够诱导体外产生的静息CD 4（+）CXCR 4（-）CCR 7（+）记忆T细胞上的功能性CXCR 4表面表达。细胞因子介导的CXCR 4表达诱导与CXCR 4转录的增加、增强的基质衍生因子-1诱导的体外T细胞迁移以及这些细胞对HIV-1的X4株感染的易感性增加相关。CD 34（+）祖细胞衍生的树突状细胞。尽管这些树突状细胞表达IL-7和IL-15的转录物，但加入中和性抗IL-7 R和IL-15 mAb并不能阻断CXCR 4表达的诱导。事实上，树突状细胞介导的CXCR 4表达上调依赖于CD 40/CD 154和CD 134/CD 134 L相互作用。尽管活化的自体树突状细胞诱导CXCR 4和CD 25在一部分CCR 7（+）记忆T细胞上的表达，伴随的CD 3介导的这些细胞的活化进一步增强CD 25表达，但相反，阻止CXCR 4表达的诱导。这一观察结果表明，与TCR/CD 3复合物介导的刺激相反，触发CD 134和CD 154分子导致同时的T细胞活化和CXCR 4表达。总之，这些结果表明，共同的γ链相互作用的细胞因子，以及通过非同源的相互作用激活的树突状细胞和记忆T细胞介导的信号参与CXCR 4表达的上调。
In the present study, we show that IL-2, IL-4, IL-7, and IL-15 are able to induce functional CXCR4 surface expression on resting in vitro-generated CD4(+) CXCR4(-) CCR7(+) memory T cells. Cytokine-mediated induction of CXCR4 expression was associated with an increase in CXCR4 transcription, enhanced stromal-derived factor-1-induced T cell migration in vitro, and increased susceptibility of these cells to infection with X4 strains of HIV-1, CXCR4 expression could also be induced through an alternative pathway, following coculture of these cells with CD40-activated, autologous, CD34(+) progenitor-derived dendritic cells. Although these dendritic cells express transcripts for IL-7 and IL-15, addition of neutralizing anti-IL-7R and IL-15 mAbs did not block induction of CXCR4 expression. Indeed, dendritic cell-mediated up-regulation of CXCR4 expression was found to depend on CD40/CD154 and CD134/CD134L interactions. Whereas activated autologous dendritic cells induced the expression of both CXCR4 and CD25 on a portion of CCR7(+) memory T cells, concomitant CD3-mediated activation of these cells further enhanced CD25 expression, but, in contrast, prevented induction of CXCR4 expression. This observation suggests that triggering of the CD134 and CD154 molecules, in contrast to TCR/CD3 complex-mediated stimulation, results in simultaneous T cell activation and CXCR4 expression. Taken together, these results show that common gamma-chain-interacting cytokines as well as signals mediated via noncognate interactions between activated dendritic cells and memory T cells are involved in the up-regulation of CXCR4 expression.