title: Peripheral expression of self-MHC-II influences the reactivity and self-tolerance of mature CD4(+) T cells: evidence from a lymphopenic T cell model.
abstract: While intrathymic MHC expression influences the specificity of developing thymocytes, we considered that peripheral MHC expression might influence the reactivity of postthymic T cells. We now report for CD4(+) T cells that peripheral MHC-II expression does influence their reactivity and self-tolerance. Upon transfer into MHC-II-deficient lymphopenic hosts, mature CD4(+) T cells were found to acquire an activated memory phenotype and to become: (1) autoreactive against syngeneic MHC-II(+) skin grafts, (2) hyperreactive against third-party MHC-II(+) skin grafts, and (3) functionally dysregulated, resulting in a lymphoproliferative disorder characterized by intraepithelial infiltrations. Peripheral MHC-II expression appeared to influence CD4(+) T cell reactivity by two complementary mechanisms: maintenance of CD4(+)CD25(+) regulatory T cells ("suppression") and direct dampening of CD4(+) T cell reactivity ("tuning").
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Avinash
authors.initials: A
authors.lastname: Bhandoola
authors.forename: Xuguang
authors.initials: X
authors.lastname: Tai
authors.forename: Michael
authors.initials: M
authors.lastname: Eckhaus
authors.forename: Hugh
authors.initials: H
authors.lastname: Auchincloss
authors.forename: Karen
authors.initials: K
authors.lastname: Mason
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rubin
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Carbone
authors.forename: Zvi
authors.initials: Z
authors.lastname: Grossman
authors.forename: Amy S
authors.initials: AS
authors.lastname: Rosenberg
authors.forename: Alfred
authors.initials: A
authors.lastname: Singer
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000378:metabolism*; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008231:Lymphopenia / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D017634:Self Tolerance; D016038:Skin Transplantation / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D014185:Transplantation, Isogeneic
chemical_list: D001324:Autoantigens; D000949:Histocompatibility Antigens Class II