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CCR1/CCL5 (RANTES) receptor-ligand interactions modulate allogeneic T-cell responses and graft-versus-host disease following stem-cell transplantation.

TitleCCR1/CCL5 (RANTES) receptor-ligand interactions modulate allogeneic T-cell responses and graft-versus-host disease following stem-cell transplantation.
Publication TypeJournal Article
Year of Publication2007
AuthorsChoi, SW, Hildebrandt, GC, Olkiewicz, KM, Hanauer, DA, Chaudhary, MN, Silva, IA, Rogers, CE, Deurloo, DT, Fisher, JM, Liu, C, Adams, D, Chensue, SW, Cooke, KR
JournalBlood
Volume110
Issue9
Pagination3447-55
Date Published2007 Nov 1
ISSN0006-4971
KeywordsAnimals, Chemokine CCL5, Gene Expression Regulation, Graft vs Host Disease, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Protein Binding, Receptors, CCR1, Stem Cell Transplantation, Survival Analysis, T-Lymphocytes, Transplantation, Homologous
Abstract

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 IFNgamma 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.

DOI10.1182/blood-2007-05-087403
Alternate JournalBlood
PubMed ID17641205
PubMed Central IDPMC2200916
Grant List5R01 HL 072258-04 / HL / NHLBI NIH HHS / United States
People: 
David Hanauer
University of Michigan Comprehensive Cancer Center at North Campus Reserach Complex
1600 Huron Parkway, Bldg 100, Rm 100 
Mailing Address: 2800 Plymouth Rd, NCRC 100-1004
Ann Arbor, MI 48109-2800 
Ph. (734) 764-8848 Fax. (734) 615-0517
Please acknowledge the Cancer Center Support Grant (P30 CA046592) when publishing manuscripts or abstracts that utilized the services of the University of Michigan's Comprehensive Cancer Center's Shared Resource: Cancer Informatics.
Suggested language: "Research reported in this [publication/press release] was supported by the National Cancer Institute of the National Institutes of Health under award number P30CA046592."

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