title: CD4+ T cells mediate murine syngeneic graft-versus-host disease-associated colitis.
abstract: Syngeneic graft-vs-host disease (SGVHD) develops following lethal irradiation, reconstitution with syngeneic bone marrow, and treatment with a 21-day course of the immunosuppressive agent cyclosporin A (CsA). Following cessation of CsA, this inducible disease is characterized by weight loss, diarrhea, and development of inflammation in the colon and liver. Although nonspecific effector cells and Th1 cytokines have been shown to participate in disease induction, the role of T cells has not been fully elucidated. Initial studies demonstrated significant increases in CD4+ T cells, but not other T cell populations in the colons of diseased animals relative to transplant control animals. To demonstrate a functional linkage between increases in colonic CD4+ T cells and disease induction, in vivo T cell depletion studies were performed. Beginning on the day of bone marrow transplantation, groups of control and CsA-treated animals were treated with mAb against either CD4 or CD8 for 21 days. Treatment with anti-CD4, but not anti-CD8, eliminated clinical symptoms and colon pathology. Interestingly, neither anti-CD4 nor anti-CD8 therapy affected the development of liver pathology associated with SGVHD. These findings demonstrated that CD4+ T cells initiate development of the intestinal inflammation associated with murine SGVHD.
authors.affiliation: Department of Internal Medicine, Markey Cancer Center, Chandler Medical Center, University of Kentucky, Lexington, KY 40536, USA. jsbrys@uky.edu
authors.forename: J Scott
authors.initials: JS
authors.lastname: Bryson
authors.forename: Lining
authors.initials: L
authors.lastname: Zhang
authors.forename: Sarah W
authors.initials: SW
authors.lastname: Goes
authors.forename: C Darrell
authors.initials: CD
authors.lastname: Jennings
authors.forename: Betty E
authors.initials: BE
authors.lastname: Caywood
authors.forename: Sonia L
authors.initials: SL
authors.lastname: Carlson
authors.forename: Alan M
authors.initials: AM
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D003092:Colitis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D016572:Cyclosporine / Q000008:administration & dosage; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008212:Lymphocyte Depletion; D051379:Mice; D008809:Mice, Inbred C3H; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014185:Transplantation, Isogeneic
chemical_list: D000911:Antibodies, Monoclonal; D016572:Cyclosporine