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This Article Full Text Full Text (PDF) 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 Hartwig, U. F. Articles by Huber, C. Search for Related Content PubMed PubMed Citation Articles by Hartwig, U. F. Articles by Huber, C. Related Collections Transplantation Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 April 2002, Vol. 99, No. 8, pp. 3041-3049 TRANSPLANTATION Murine acute graft-versus-host disease can be prevented by depletion of alloreactive T lymphocytes using activation-induced cell death Udo F. Hartwig, Michael Robbers, Claudia Wickenhauser, and Christoph Huber From the Division of Hematology, III Department of Medicine, University Medical School Mainz, Germany; and Institute of Pathology, University of Cologne, Germany. Depletion of T lymphocytes from allogeneic bone marrow transplants successfully prevents the development of graft-versus-host disease (GvHD) but is associated with impaired engraftment, immunosuppression, and abrogation of the graft-versus-leukemia effect. We therefore explored the possibility of selectively eliminating alloreactive T cells by CD95/CD95L-mediated activation-induced cell death (AICD) in a major histocompatibility complex allogeneic murine model system. Activation of resting or preactivated T lymphocytes from C3H/HeJ (H-2k) mice was induced with irradiated BALB/cJ (H-2d) mouse-derived stimulators. Substantial decrease ( 80%) of proliferative and lytic responses by activated alloreactive T cells was subsequently achieved by incubating the mixed lymphocyte culture with an agonistic monoclonal antibody to CD95, and residual T cells recovered did not elicit alloreactivity upon challenge to H-2d. Depletion of alloreactive T lymphocytes by AICD was specific because reactivity to an I-Ad-restricted ovalbumin (OVA) peptide by OVA-specific CD4+ T cells mixed into the allogeneic T-cell pool and subjected to induction of AICD in the absence of OVA peptide could be preserved. Adoptive transfer of donor-derived allogeneic T lymphocytes, depleted from alloreactive T cells by AICD in vitro, in the parent (C3H/He) to F1 (C3H/He × BALB/c) GvHD model prevented lethal GvHD. The results presented suggest that alloreactive T cells can effectively be depleted from allogeneic T cells by induction of AICD to prevent GvHD and might introduce a new strategy for the separation of GvH-reactive T cells and T cells mediating antiviral and possibly graft-versus-leukemia effects. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Mielke, R. Nunes, K. Rezvani, V. S. Fellowes, A. Venne, S. R. Solomon, Y. Fan, E. Gostick, D. A. Price, C. Scotto, et al. A clinical-scale selective allodepletion approach for the treatment of HLA-mismatched and matched donor-recipient pairs using expanded T lymphocytes as antigen-presenting cells and a TH9402-based photodepletion technique Blood, April 15, 2008; 111(8): 4392 - 4402. [Abstract] [Full Text] [PDF] S. Mielke, K. Rezvani, B. N. Savani, R. Nunes, A. S. M. Yong, J. Schindler, R. Kurlander, V. Ghetie, E. J. Read, S. R. Solomon, et al. Reconstitution of FOXP3+ regulatory T cells (Tregs) after CD25-depleted allotransplantion in elderly patients and association with acute graft-versus-host disease Blood, September 1, 2007; 110(5): 1689 - 1697. [Abstract] [Full Text] [PDF] T. C. Wehler, M. Nonn, B. Brandt, C. M. Britten, M. Grone, M. Todorova, I. Link, S. A. Khan, R. G. Meyer, C. Huber, et al. Targeting the activation-induced antigen CD137 can selectively deplete alloreactive T cells from antileukemic and antitumor donor T-cell lines Blood, January 1, 2007; 109(1): 365 - 373. [Abstract] [Full Text] [PDF] S. R. Solomon, S. Mielke, B. N. Savani, A. Montero, L. Wisch, R. Childs, N. Hensel, J. Schindler, V. Ghetie, S. F. Leitman, et al. Selective depletion of alloreactive donor lymphocytes: a novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation Blood, August 1, 2005; 106(3): 1123 - 1129. 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Solomon, A. M. Dickinson, X. N. Wang, G. Stark, H. Cullup, M. Jarvis, P. G. Middleton, and N. Chao New Developments in Allotransplant Immunology Hematology, January 1, 2003; 2003(1): 350 - 371. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020