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Blood, 1 December 2004, Vol. 104, No. 12, pp. 3429-3436. Prepublished online as a Blood First Edition Paper on July 29, 2004; DOI 10.1182/blood-2004-05-1918. This Article Full Text (PDF) All Versions of this Article: 2004-05-1918v1 104/12/3429    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 Martins, S. L Articles by Komanduri, K. V Search for Related Content PubMed PubMed Citation Articles by Martins, S. L Articles by Komanduri, K. V Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 20, 2004 Accepted July 12, 2004 Functional assessment and specific depletion of alloreactive human T cells using flow cytometry Sergio L Martins, Lisa S St. John, Richard E Champlin, Eric D Wieder, John McMannis, Jeffrey J Molldrem, and Krishna V Komanduri* Transplant Immunology Section, Dept. of Blood and Marrow Transplantation, M.D. Anderson Cancer Center, Houston, TX, USA; Department of Hematology, Fleury-Diagnostic Medical Center, Sao Paolo, Brazil Transplant Immunology Section, Dept. of Blood and Marrow Transplantation, M.D. Anderson Cancer Center, Houston, TX, USA * Corresponding author; email: kkomandu{at}mdanderson.org. Human T cell alloreactivity plays an important role in many disease processes, including the rejection of solid organ grafts and graft-versus-host disease (GVHD) following allogeneic stem cell transplantation. To develop a better understanding of the T cells involved in alloreactivity in humans, we developed a cytokine flow cytometry (CFC) assay that enabled us to characterize the phenotypic and functional characteristic of T cells responding to allogeneic stimuli. Using this approach, we determined that most T cell alloreactivity resided within the CD4+ T cell subset, as assessed by activation marker expression and the production of effector cytokines (e.g., TNF) implicated in human GVHD. Following prolonged stimulation in vitro using either allogeneic stimulator cells or viral antigens, we found that co-expression of activation markers within the CD4+ T cell subset occurred exclusively within a subpopulation of T cells that significantly increased their surface expression of CD4. We then developed a simple sorting strategy that exploited these phenotypic characteristics to specifically deplete alloreactive T cells, while retaining broad specificity for other stimuli, including viral antigens and third party alloantigens. This approach was also applied to specifically enrich or deplete human virus-specific T cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Depletion of alloreactive T cells: which cell? Sherif S. Farag Blood 2004 104: 3422-3423. [Full Text] [PDF] This article has been cited by other articles: S. Samarasinghe, C. Mancao, M. Pule, N. Nawroly, H. Karlsson, J. Brewin, P. Openshaw, H. B. Gaspar, P. Veys, and P. J. Amrolia Functional characterization of alloreactive T cells identifies CD25 and CD71 as optimal targets for a clinically applicable allodepletion strategy Blood, January 14, 2010; 115(2): 396 - 407. [Abstract] [Full Text] [PDF] O. Bohana-Kashtan, S. Morisot, R. Hildreth, C. Brayton, H. I. Levitsky, and C. I. Civin Selective Reduction of Graft-versus-Host Disease-Mediating Human T Cells by Ex Vivo Treatment with Soluble Fas Ligand J. Immunol., July 1, 2009; 183(1): 696 - 705. [Abstract] [Full Text] [PDF] T. M. Friedman, K. Goldgirsh, S. A. Berger, J. Zilberberg, J. Filicko-O'Hara, N. Flomenberg, M. Donato, S. D. Rowley, and R. Korngold Overlap between in vitro donor antihost and in vivo posttransplantation TCR V{beta} use: a new paradigm for designer allogeneic blood and marrow transplantation Blood, October 15, 2008; 112(8): 3517 - 3525. [Abstract] [Full Text] [PDF] K. Sun, M. Li, T. J. Sayers, L. A. Welniak, and W. J. Murphy Differential effects of donor T-cell cytokines on outcome with continuous bortezomib administration after allogeneic bone marrow transplantation Blood, August 15, 2008; 112(4): 1522 - 1529. [Abstract] [Full Text] [PDF] 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] Z. Fan, X.-L. Huang, P. Kalinski, S. Young, and C. R. Rinaldo Jr. Dendritic Cell Function during Chronic Hepatitis C Virus and Human Immunodeficiency Virus Type 1 Infection Clin. Vaccine Immunol., September 1, 2007; 14(9): 1127 - 1137. [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] P. J. Amrolia, G. Muccioli-Casadei, H. Huls, S. Adams, A. Durett, A. Gee, E. Yvon, H. Weiss, M. Cobbold, H. B. Gaspar, et al. Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation Blood, September 15, 2006; 108(6): 1797 - 1808. [Abstract] [Full Text] [PDF] E. Landais, A. Morice, H. M. Long, T. A. Haigh, B. Charreau, M. Bonneville, G. S. Taylor, and E. Houssaint EBV-Specific CD4+ T Cell Clones Exhibit Vigorous Allogeneic Responses J. Immunol., August 1, 2006; 177(3): 1427 - 1433. [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. [Abstract] [Full Text] [PDF]

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