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The Journal of Immunology, 2004, 172: 6123-6128.
Copyright © 2004 by The American Association of Immunologists

Human CD4+CD25+ Regulatory T Cells Share Equally Complex and Comparable Repertoires with CD4+CD25– Counterparts 1

Kimberly A. Kasow, Xiaohua Chen, James Knowles, David Wichlan, Rupert Handgretinger and Janice M. Riberdy2

Division of Stem Cell Transplantation, St. Jude Children’s Research Hospital, Memphis, TN 38105

CD4+CD25+ T cells are critical mediators of peripheral immune tolerance. However, many developmental and functional characteristics of these cells are unknown, and knowledge of human regulatory T cells is particularly limited. To better understand how human CD4+CD25+ T cells develop and function, we examined the diversity of CD4+CD25+ and CD4+CD25– T cell repertoires in both thymus and peripheral blood. Levels of T receptor excision circles (TREC) were comparable in purified CD4+CD25+ and CD4+CD25– thymic populations, but were significantly higher than those in samples derived from peripheral blood, consistent with murine studies demonstrating thymic development of CD4+CD25+ regulatory T cells. Surprisingly, CD4+CD25– T cells isolated from peripheral blood had greater TREC quantities than their CD4+CD25+ counterparts, supporting the possibility of extrathymic expansion as well. CD4+CD25+ and CD4+CD25– T cells from a given individual showed overlapping profiles with respect to diversity by V{beta} staining and spectratyping. Interestingly, CD4+CD25+ T cells have lower quantities of CD3 than CD4+CD25– T cells. Collectively, these data suggest that human CD4+CD25+ T cells recognize a similar array of Ags as CD4+CD25– T cells. However, reduced levels of TCR on regulatory T cells suggest different requirements for activation and may contribute to how the immune system regulates whether a particular response is suppressed or augmented.




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