Chemokine receptor CCR5 mediates alloimmune responses in graft-versus-host disease.
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.
Palmer
Lisa A
LA
Section of Transplantation Immunology, Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Sale
George E
GE
Balogun
John I
JI
Li
Dan
D
Jones
Dan
D
Molldrem
Jeffrey J
JJ
Storb
Rainer F
RF
Ma
Qing
Q
D018949:Antigens, CD1 / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007801:Langerhans Cells / Q000378:metabolism / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008046:Lip / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D019713:Receptors, CCR5 / Q000378:metabolism*; D012867:Skin / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D014181:Transplantation Immunology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018949:Antigens, CD1; C419393:CD1a antigen; D007376:Interleukin-2; D019713:Receptors, CCR5; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma