Michaëlsson Jakob, Mold Jeff E, McCune Joseph M, Nixon Douglas F
Gladstone Institute of Virology and Immunology, University of California-San Francisco, 1001 Potrero Avenue, San Francisco, CA 94158, USA.
J Immunol. 2006 May 15;176(10):5741-8. doi: 10.4049/jimmunol.176.10.5741.
Although human T cells enter the peripheral lymphoid tissues early during fetal development, the adaptive immune system in the fetus has largely been regarded as functionally immature and unresponsive to stimulation. In this study, we show that depletion of fetal CD4+CD25(high) T regulatory (T(Reg)) cells, which are present at high frequency in fetal lymphoid tissues, results in vigorous T cell proliferation and cytokine production in vitro, even in the absence of exogenous stimulation. Analysis of CD4+ and CD8(+) T cell populations revealed a large subset of cells that expressed the early activation Ag, CD69. We show that this population represents a subset of highly reactive fetal T cells actively suppressed by fetal CD4+CD25(high) T(Reg) cells during development. These findings indicate that fetal T cells are, in the absence of CD4+CD25(high) T(Reg) cells, highly responsive to stimulation and provide evidence for an important role for CD4+CD25(high) T(Reg) cells in controlling T cell responses in utero.
尽管人类T细胞在胎儿发育早期就进入外周淋巴组织，但胎儿的适应性免疫系统在很大程度上被认为功能不成熟且对刺激无反应。在本研究中，我们发现胎儿CD4+CD25（高）调节性T（Treg）细胞在胎儿淋巴组织中高频存在，去除这些细胞会导致体外T细胞剧烈增殖和细胞因子产生，即使在没有外源性刺激的情况下也是如此。对CD4+和CD8+T细胞群体的分析揭示了一大群表达早期激活抗原CD69的细胞。我们表明，这群细胞代表了在发育过程中被胎儿CD4+CD25（高）Treg细胞积极抑制的高反应性胎儿T细胞亚群。这些发现表明，在没有CD4+CD25（高）Treg细胞的情况下，胎儿T细胞对刺激高度敏感，并为CD4+CD25（高）Treg细胞在子宫内控制T细胞反应中的重要作用提供了证据。
