title: The host response in graft versus host disease. III. The in vitro induction of regulatory cells in chronic murine graft versus host disease.
abstract: Murine graft versus host (GVH) disease takes two forms depending upon the parental/F1 strain combination employed. Acute lethal GVH disease is characterized by anemia, lymphopenia, hypogammaglobulinemia, profound anti-F1 cytotoxicity, and the loss of cytotoxic potential against third-party alloantigen. In contrast to this, chronic GVH disease is characterized by polyclonal B cell activation, autoantibody production, no anti-F1 cytotoxicity, and retained cytotoxicity against allotargets. We have previously reported that this marked disparity in disease expression results from a radiosensitive host cell which protects the F1 mouse from parental anti-F1 CTX in mice undergoing CGVH disease. Using an in vitro system to induce the host protective cell, we now demonstrate that two distinct Thy-1+ cells emerge which regulate CTX against the host. One cell is of host origin, radiation sensitive, and functionally resembles a veto cell. The second regulatory cell, of parental origin, is radiation resistant and restricted in its ability to suppress anti-F1 CTX. We further demonstrate that the emergence of these cells is modulated by competitive immunoregulatory influences mediated by T contrasuppressor and I-J+ cells.
authors.affiliation: Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Mann
authors.forename: A B
authors.initials: AB
authors.lastname: Singh
authors.forename: A E
authors.initials: AE
authors.lastname: Jetzt
authors.forename: M
authors.initials: M
authors.lastname: Singh
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000528:radiation effects; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000949:Histocompatibility Antigens Class II; D011838:Radiation-Sensitizing Agents