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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3970-3978. Prepublished online as a Blood First Edition Paper on February 5, 2004; DOI 10.1182/blood-2003-09-3135. This Article Full Text (PDF) All Versions of this Article: 2003-09-3135v1 103/10/3970    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 Zhang, Y. Articles by Emerson, S. G Search for Related Content PubMed PubMed Citation Articles by Zhang, Y. Articles by Emerson, S. G Social Bookmarking                   What's this? Submitted September 15, 2003 Accepted January 21, 2004 Dendritic Cell Activated CD44hiCD8+ T Cells Are Defective in Mediating Acute Graft-versus-host Disease but Retain Graft-versus-leukemia Activity Yi Zhang, Gerard Joe, Jiang Zhu, Richard Carroll, Bruce Levine, Elizabeth Hexner, Carl June, and Stephen G Emerson* Department of Medicine and Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA Department of Pathology and Laboratory Medicine and Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA, USA * Corresponding author; email: emersons{at}mail.med.upenn.edu. Graft versus host disease (GVHD) is triggered by host antigen presenting cells (APCs) that activate donor T cells to proliferate and differentiate, but which APC-activated donor T cell subsets mediate GVHD versus beneficial anti-tumor effects is not known. Using a CD8+ T cell dependent mouse model of human GVHD, we found that host dendritic cell (DC)-induced CD44hiCD8+ effector/memory T cells were functionally defective in inducing GVHD, whereas CD44loCD8+ naive phenotype T cells were extremely potent GVHD inducers. Depletion of CD44loCD8+ T cells from host DC-stimulated T cells before transplantation prevented GVHD without impairing their anti-tumor activity in vivo. Compared with CD44loCD8+ T cells, CD44hiCD8+ T cells expressed high levels of Fas and were efficiently deleted in vivo following transplantation. These results suggest that ex vivo allogeneic DC stimulation of donor CD8+ T cells may be useful for the prevention of GVHD, and for optimizing anti-tumor therapies in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Zheng, C. Matte-Martone, D. Jain, J. McNiff, and W. D. Shlomchik Central Memory CD8+ T Cells Induce Graft-versus-Host Disease and Mediate Graft-versus-Leukemia J. Immunol., May 15, 2009; 182(10): 5938 - 5948. [Abstract] [Full Text] [PDF] S. He, Q. Cao, Y. Qiu, J. Mi, J. Z. Zhang, M. Jin, H. Ge, S. G. Emerson, Y. Zhang, and Y. Zhang A New Approach to the Blocking of Alloreactive T Cell-Mediated Graft-versus-Host Disease by In Vivo Administration of Anti-CXCR3 Neutralizing Antibody J. Immunol., December 1, 2008; 181(11): 7581 - 7592. [Abstract] [Full Text] [PDF] B. E. Anderson, P. A. Taylor, J. M. McNiff, D. Jain, A. J. Demetris, A. Panoskaltsis-Mortari, A. Ager, B. R. Blazar, W. D. Shlomchik, and M. J. Shlomchik Effects of donor T-cell trafficking and priming site on graft-versus-host disease induction by naive and memory phenotype CD4 T cells Blood, May 15, 2008; 111(10): 5242 - 5251. [Abstract] [Full Text] [PDF] H. Zheng, C. Matte-Martone, H. Li, B. E. Anderson, S. Venketesan, H. Sheng Tan, D. Jain, J. McNiff, and W. D. Shlomchik Effector memory CD4+ T cells mediate graft-versus-leukemia without inducing graft-versus-host disease Blood, February 15, 2008; 111(4): 2476 - 2484. [Abstract] [Full Text] [PDF] Y. Zhang, E. Hexner, D. Frank, and S. G. Emerson CD4+ T Cells Generated De Novo from Donor Hemopoietic Stem Cells Mediate the Evolution from Acute to Chronic Graft-versus-Host Disease J. Immunol., September 1, 2007; 179(5): 3305 - 3314. [Abstract] [Full Text] [PDF] B. J. Chen, D. Deoliveira, X. Cui, N. T. Le, J. Son, J. F. Whitesides, and N. J. Chao Inability of memory T cells to induce graft-versus-host disease is a result of an abortive alloresponse Blood, April 1, 2007; 109(7): 3115 - 3123. [Abstract] [Full Text] [PDF] A. Chorny, E. Gonzalez-Rey, A. Fernandez-Martin, D. Ganea, and M. Delgado Vasoactive intestinal peptide induces regulatory dendritic cells that prevent acute graft-versus-host disease while maintaining the graft-versus-tumor response Blood, May 1, 2006; 107(9): 3787 - 3794. [Abstract] [Full Text] [PDF] M. Ohashi, A. Kobayashi, H. Hara, Y. Miura, K. Yoshida, M. Kushida, Y. Ikarashi, M. Mandai, M. Kitajima, T. Yoshida, et al. Allogeneic MHC gene transfer enhances antitumor activity of allogeneic hematopoietic stem cell transplantation without exacerbating graft-versus-host disease. Clin. Cancer Res., April 1, 2006; 12(7 Pt 1): 2208 - 2215. [Abstract] [Full Text] [PDF] A. Beilhack, S. Schulz, J. Baker, G. F. Beilhack, C. B. Wieland, E. I. Herman, E. M. Baker, Y.-A. Cao, C. H. Contag, and R. S. Negrin In vivo analyses of early events in acute graft-versus-host disease reveal sequential infiltration of T-cell subsets Blood, August 1, 2005; 106(3): 1113 - 1122. [Abstract] [Full Text] [PDF] Y. Zhang, G. Joe, E. Hexner, J. Zhu, and S. G. Emerson Alloreactive Memory T Cells Are Responsible for the Persistence of Graft-versus-Host Disease J. Immunol., March 1, 2005; 174(5): 3051 - 3058. [Abstract] [Full Text] [PDF]

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