Peripheral expression of self-MHC-II influences the reactivity and self-tolerance of mature CD4(+) T cells: evidence from a lymphopenic T cell model.
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").
Bhandoola
Avinash
A
Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Tai
Xuguang
X
Eckhaus
Michael
M
Auchincloss
Hugh
H
Mason
Karen
K
Rubin
Steven A
SA
Carbone
Kathryn M
KM
Grossman
Zvi
Z
Rosenberg
Amy S
AS
Singer
Alfred
A
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
D001324:Autoantigens; D000949:Histocompatibility Antigens Class II