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Blood, 15 January 2008, Vol. 111, No. 2, pp. 945-953. Prepublished online as a Blood First Edition Paper on October 4, 2007; DOI 10.1182/blood-2007-07-103895. This Article Full Text (PDF) All Versions of this Article: blood-2007-07-103895v1 111/2/945    most recent Alert me when this article is cited Alert me if a correction is posted 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 Nguyen, V. H Articles by Negrin, R. S. Search for Related Content PubMed PubMed Citation Articles by Nguyen, V. H Articles by Negrin, R. S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 27, 2007 Accepted September 28, 2007 The impact of regulatory T cells on T cell immunity following hematopoeitic cell transplantation Vu H Nguyen, Sumama Shashidhar, Daisy S Chang, Lena Ho, Neeraja Kambham, Michael Bachmann, Janice M Brown, and Robert S. Negrin* Dept of Medicine, Division of Bone Marrow Transplantation, Stanford University, Stanford, CA, United States Program in Immunology, Stanford University, Stanford, CA, United States Department of Pathology, Stanford University, Stanford, CA, United States Department of Pediatrics, Stanford University, Stanford, CA, United States * Corresponding author; email: negrs{at}stanford.edu. Regulatory T cells (Treg) prevent graft-versus-host disease (GvHD) by inhibiting the proliferation and function of conventional T cells (Tcon). However, the impact of Treg on T cell development and immunity following hematopoietic cell transplantation (HCT) is unknown. Using a murine GvHD model induced by Tcon, we demonstrate that adoptive transfer of Treg leads to (1) abrogration of GvHD; (2) preservation of thymic and peripheral lymph node architecture; and (3) an accelerated donor lymphoid reconstitution of a diverse TCR-V repertoire. The resultant enhanced lymphoid reconstitution in Treg recipients protects them from lethal cytomegalovirus (MCMV) infection. By contrast, mice that receive Tcon alone have disrupted lymphoid organs from GvHD and remain lymphopenic with a restricted TCR-V repertoire and rapid death upon MCMV challenge. Lymphocytes from previously infected Treg recipients generate secondary response specific to MCMV, indicating long-term protective immunity with transferred Treg. Thymectomy significantly reduces survival after MCMV challenge in Treg recipients compared to euthymic controls. Our results indicate that Treg enhance immune reconstitution by preventing GvHD-induced damage of the thymic and secondary lymphoid microenvironment. These findings provide new insights into the role of Treg in affording protection to lymphoid stromal elements important for T cell immunity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: X. Chen, R. Das, R. Komorowski, A. Beres, M. J. Hessner, M. Mihara, and W. R. Drobyski Blockade of interleukin-6 signaling augments regulatory T-cell reconstitution and attenuates the severity of graft-versus-host disease Blood, July 23, 2009; 114(4): 891 - 900. [Abstract] [Full Text] [PDF] W. Tu, Y.-L. Lau, J. Zheng, Y. Liu, P.-L. Chan, H. Mao, K. Dionis, P. Schneider, and D. B. Lewis Efficient generation of human alloantigen-specific CD4+ regulatory T cells from naive precursors by CD40-activated B cells Blood, September 15, 2008; 112(6): 2554 - 2562. [Abstract] [Full Text] [PDF]

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