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* Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94158;
Biomedical Sciences Graduate Program, University of California, San Francisco, CA 94143; and
Department of Medicine, University of California, San Francisco, CA 94110
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+CD25high T regulatory (TReg) 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+CD25high TReg cells during development. These findings indicate that fetal T cells are, in the absence of CD4+CD25high TReg cells, highly responsive to stimulation and provide evidence for an important role for CD4+CD25high TReg cells in controlling T cell responses in utero.
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