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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3447-3455. Prepublished online as a Blood First Edition Paper on July 19, 2007; DOI 10.1182/blood-2007-05-087403. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-05-087403v1 110/9/3447    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Choi, S. W. Articles by Cooke, K. R. Search for Related Content PubMed PubMed Citation Articles by Choi, S. W. Articles by Cooke, K. R. Related Collections Transplantation Chemokines, Cytokines, and Interleukins Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION CCR1/CCL5 (RANTES) receptor-ligand interactions modulate allogeneic T-cell responses and graft-versus-host disease following stem-cell transplantation Sung W. Choi1, Gerhard C. Hildebrandt1,2, Krystyna M. Olkiewicz1, David A. Hanauer3, Meghana N. Chaudhary1, Ines A. Silva1, Clare E. Rogers1, Daphne T. Deurloo1, Jacki M. Fisher1, Chen Liu4, David Adams5, Stephen W. Chensue6, and Kenneth R. Cooke1 1 Department of Pediatrics, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor; 2 Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany; 3 Cancer Center Bioinformatics Core, University of Michigan, Ann Arbor; 4 Department of Pathology, University of Florida School of Medicine, Gainesville; 5 Cancer Center Flow Cytometry Core, University of Michigan, Ann Arbor; and 6 Department of Pathology, University of Michigan, Ann Arbor Acute graft-versus-host disease (GVHD) and leukemic relapse are serious complications of allogeneic stem-cell transplantation (SCT). Recruitment of activated T cells to host target tissues or sites of leukemic infiltration (graft-versus-leukemia [GVL]) is likely mediated by chemokine receptor–ligand interactions. We examined the contribution of donor cell CCR1 expression to the development of GVHD and GVL using a well-established murine SCT model (B6 B6D2F1) and CCR1-deficient mice (CCR1–/–). Allo-SCT with CCR1–/– donor cells significantly reduced systemic and target organ GVHD severity, and CCR1 expression on both T cells and accessory cells contributed to GVHD mortality. Significant GVL activity was preserved following CCR1–/– SCT, but the survival advantage diminished with increasing tumor burden. We then explored the effects of CCR1 expression on allo-specific T-cell responses. Although cytolytic effector function was maintained on a per-cell basis, T-cell proliferation and IFN secretion were significantly reduced both in vivo and in vitro. T-cell function was partially dependent on interactions between CCR1 and CCL5. Collectively, these data demonstrate that CCR1 expression on donor cells contributes to the development of both GVHD and GVL, and suggest that CCR1/CCL5 receptor-ligand interactions modulate allo-specific T-cell responses occurring in this context. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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