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Blood, 1 May 2007, Vol. 109, No. 9, pp. 4071-4079. Prepublished online as a Blood First Edition Paper on December 29, 2006; DOI 10.1182/blood-2006-10-050625. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-10-050625v1 109/9/4071    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhang, D. Articles by Zheng, X. X. Search for Related Content PubMed PubMed Citation Articles by Zhang, D. Articles by Zheng, X. X. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION New differentiation pathway for double-negative regulatory T cells that regulates the magnitude of immune responses Dong Zhang1,2, Wei Yang1, Nicolas Degauque1, Yan Tian1, Allison Mikita1, and Xin Xiao Zheng1 1 Transplantation Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston MA; 2 Capital University of Medical Sciences, Beijing Friendship Hospital, Beijing, China Recent studies have demonstrated that in peripheral lymphoid tissues of normal mice and healthy humans, 1% to 5% of ß T-cell receptor–positive (TCR+) T cells are CD4–CD8– (double-negative [DN]) T cells, capable of down-regulating immune responses. However, the origin and developmental pathway of DN T cells is still not clear. In this study, by monitoring CD4 expression during T-cell proliferation and differentiation, we identified a new differentiation pathway for the conversion of CD4+ T cells to DN regulatory T cells. We showed that the converted DN T cells retained a stable phenotype after restimulation and that furthermore, the disappearance of cell-surface CD4 molecules on converted DN T cells was a result of CD4 gene silencing. The converted DN T cells were resistant to activation-induced cell death (AICD) and expressed a unique set of cell-surface markers and gene profiles. These cells were highly potent in suppressing alloimmune responses both in vitro and in vivo in an antigen-specific manner. Perforin was highly expressed by the converted DN regulatory T cells and played a role in DN T-cell–mediated suppression. Our findings thus identify a new differentiation pathway for DN regulatory T cells and uncover a new intrinsic homeostatic mechanism that regulates the magnitude of immune responses. This pathway provides a novel, cell-based, therapeutic approach for preventing allograft rejection. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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