Chemokine receptor CCR5 mediates alloimmune responses in graft-versus-host disease.

Publication Type:

Journal Article

Source:

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, Volume 16, Issue 3, p.311-9 (2010)

Keywords:

2010, Antigens, CD1, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Proliferation, Center-Authored Paper, Clinical Research Division, Comparative Medicine Core Facility, DENDRITIC CELLS, Experimental Histopathology Core Facility, Graft vs Host Disease, Humans, interferon-gamma, Interleukin-2, Langerhans Cells, Leukocytes, Mononuclear, Lip, Lymphocyte Activation, Lymphocyte Culture Test, Mixed, Receptors, CCR5, Research Trials Office Core Facility - Biostatistics Service, Shared Resources, Skin, T-Lymphocytes, Transplantation Immunology, Tumor Necrosis Factor-alpha

Abstract:

Allogeneic bone marrow transplantation (BMT) is an effective therapy for hematologic malignancies. However graft-versus-host disease (GVHD) is a major limiting factor for a successful patient outcome. GVHD is a result of alloimmune responses of donor T lymphocytes attacking the recipient's cells and tissues. Chemokine receptor CCR5 plays a role in solid organ allograft rejection and mediates murine GVHD pathogenesis. Herein, we report that infiltrating lymphocytes in the skin of human acute GVHD (aGVHD) samples are predominantly CCR5(+) T cells. In addition, we characterized the features of the CCR5 expression on alloreactive T lymphocytes. We found that the CCR5(+) population exhibits the characteristics of the activated effector T cell phenotype. CCR5 expression is upregulated upon allogenic stimulation, and CCR5(+) cells are proliferating with coexpression of T cell activation markers. Furthermore, the activated T cells producing inflammatory cytokine tumor necrosis factor (TNF)alpha, interleukin (IL)-2, or interferon (IFN)-gamma, are positive for CCR5. Thus, CCR5 is a marker for GVHD effector cells and CCR5(+) T cells are active participants in the pathogenesis of human aGVHD.