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Blood, 15 January 2006, Vol. 107, No. 2, pp. 628-636. Prepublished online as a Blood First Edition Paper on September 22, 2005; DOI 10.1182/blood-2005-07-2737. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-07-2737v1 107/2/628    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhou, G. Articles by Levitsky, H. I. Search for Related Content PubMed PubMed Citation Articles by Zhou, G. Articles by Levitsky, H. I. Related Collections Immunotherapy Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines Gang Zhou, Charles G. Drake, and Hyam I. Levitsky From the Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD. The fate of tumor-specific CD4+ T cells is central to the outcome of the host immune response to cancer. We show that tumor antigen recognition by a subset of CD4+ T cells led to their differentiation into cells capable of suppressing naive and Th1 effector cells. Such tumor-induced regulatory T cells (TMTregs) arose both from precommitted "natural" regulatory T cells and CD4+CD25–GITRlow precursors. Once induced, TMTregs were capable of maintaining suppressor activity long after transfer into antigen-free recipients. Suppression was mediated by GITRhigh cells residing within both CD25+ and CD25– subsets. Vaccination of the tumor-bearing host concomitantly expanded TMTregs and effector cells, but suppression was dominant, blunting the expansion of naive tumor-specific T cells and blocking the execution of effector function in vitro and in vivo. These studies illustrate the possibility that therapeutic vaccination could actually worsen host tolerance to tumor antigens and support treatment paradigms that seek to not only increase the frequency of tumor-specific T cells, but to do so in conjunction with strategies that inactivate or remove regulatory T-cell populations. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Wang, K. Pino-Lagos, V. C. de Vries, I. Guleria, M. H. Sayegh, and R. J. 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