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Blood, 15 February 2008, Vol. 111, No. 4, pp. 2112-2121. Prepublished online as a Blood First Edition Paper on December 6, 2007; DOI 10.1182/blood-2007-06-096586. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-06-096586v1 111/4/2112    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 Mirmonsef, P. Articles by Levitsky, H. I. Search for Related Content PubMed PubMed Citation Articles by Mirmonsef, P. Articles by Levitsky, H. I. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Escape from suppression: tumor-specific effector cells outcompete regulatory T cells following stem-cell transplantation Paria Mirmonsef1, Gladys Tan1,2, Gang Zhou1, Tricia Morino1, Kimberly Noonan1, Ivan Borrello1, and Hyam I. Levitsky1 1 Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD; and 2 Defense Medical and Environmental Research Institute, Singapore Immune reconstitution of autologous hematopoietic stem-cell transplant recipients with the progeny of mature T cells in the graft leads to profound changes in the emerging functional T-cell repertoire. In the steady state, the host is frequently tolerant to tumor antigens, reflecting dominant suppression of naive and effector T cells by regulatory T cells (Tregs). We examined the relative frequency and function of these 3 components within the tumor-specific T-cell compartment during immune reconstitution. Grafts from tumor-bearing donors exerted a significant antitumor effect in irradiated, syngeneic tumor-bearing recipients. This was associated with dramatic clonal expansion and interferon- (IFN) production by previously tolerant tumor-specific T cells. While donor-derived Tregs expanded in recipients, they did not inhibit the antigen-driven expansion of effector T cells in the early posttransplantation period. Indeed, the repopulation of tumor-specific effector T cells significantly exceeded that of Tregs, the expansion of which was limited by IL-2 availability. Although the intrinsic suppressive capacity of Tregs remained intact, their diminished frequency was insufficient to suppress effector cell function. These findings provide an explanation for the reversal of tolerance leading to tumor rejection in transplant recipients and likely contribute to the efficacy of adoptive T-cell therapies in lymphopenic hosts. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. T. Ho, M. Vanneman, H. Kim, T. Sasada, Y. J. Kang, M. Pasek, C. Cutler, J. Koreth, E. Alyea, S. Sarantopoulos, et al. Biologic activity of irradiated, autologous, GM-CSF-secreting leukemia cell vaccines early after allogeneic stem cell transplantation PNAS, September 15, 2009; 106(37): 15825 - 15830. [Abstract] [Full Text] [PDF] I. Horkheimer, M. Quigley, J. Zhu, X. Huang, N. J. Chao, and Y. Yang Induction of type I IFN is required for overcoming tumor-specific T-cell tolerance after stem cell transplantation Blood, May 21, 2009; 113(21): 5330 - 5339. [Abstract] [Full Text] [PDF] J. D. Brody, M. J. Goldstein, D. K. Czerwinski, and R. Levy Immunotransplantation preferentially expands T-effector cells over T-regulatory cells and cures large lymphoma tumors Blood, January 1, 2009; 113(1): 85 - 94. [Abstract] [Full Text] [PDF]

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