CCR2 is required for CD8-induced graft-versus-host disease Journal Article

Authors: Terwey, T. H.; Kim, T. D.; Kochman, A. A.; Hubbard, V. M.; Lu, S.; Zakrzewski, J. L.; Ramirez-Montagut, T.; Eng, J. M.; Muriglan, S. J.; Heller, G.; Murphy, G. F.; Liu, C.; Budak-Alpdogan, T.; Alpdogan, O.; van den Brink, M. R. M.
Article Title: CCR2 is required for CD8-induced graft-versus-host disease
Abstract: Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). Migration of donor-derived T cells into GVHD target organs plays a critical role in the development of GVHD and chemokines and their receptors are important molecules involved in this process. Here, we demonstrate in murine bone marrow transplantation models that the expression of the inflammatory CC chemokine receptor 2 (CCR2) on donor-derived CD8 + T cells is relevant for the control of CD8 + T-cell migration and development of GVHD. Recipients of CCR2-deficient (CCR2 -/-) CD8 + T cells developed less damage of gut and liver than recipients of wild-type CD8 + T cells, which correlated with a reduction in overall GVHD morbidity and mortality. Assessment of donor CD8 + T-cell target organ infiltration revealed that CCR2 -/- CD8 + T cells have an intrinsic migratory defect to the gut and liver. Other causes for the reduction in GVHD could be excluded, as alloreactive proliferation, activation, IFN-γ production and cytotoxicity of CCR2 -/- CD8 + T cells were intact. Interestingly, the graft-versustumor effect mediated by CCR2 -/- CD8 + T cells was preserved, which suggests that interference with T-cell migration by blockade of CCR2 signaling can separate GVHD from GVT activity. © 2005 by The American Society of Hematology.
Keywords: signal transduction; controlled study; protein expression; survival rate; mortality; nonhuman; comparative study; cell proliferation; lymphocyte proliferation; t lymphocyte; cd8-positive t-lymphocytes; animal cell; mouse; animals; mice; mice, knockout; animal tissue; morbidity; cell line; animal experiment; animal model; cytotoxicity; wild type; liver; correlation analysis; donor; gamma interferon; thymus gland; graft versus host reaction; cell movement; cytokine production; pancytopenia; bone marrow transplantation; graft vs host disease; graft versus leukemia effect; intestines; t lymphocyte activation; chemokine receptor ccr2; receptors, chemokine; liver injury; intestine injury; antigens, cd8; alloimmunity; recipient; lymphocyte migration; interferon type ii
Journal Title: Blood
Volume: 106
Issue: 9
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2005-11-01
Start Page: 3322
End Page: 3330
Language: English
DOI: 10.1182/blood-2005-05-1860
PUBMED: 16037386
PROVIDER: scopus
PMCID: PMC1895329
Notes: --- - "Cited By (since 1996): 47" - "Export Date: 24 October 2012" - "CODEN: BLOOA" - "Source: Scopus"
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