title: CD4+ NKT cells, but not conventional CD4+ T cells, are required to generate efferent CD8+ T regulatory cells following antigen inoculation in an immune-privileged site.
abstract: Following inoculation of Ag into the anterior chamber (a.c.), systemic tolerance develops that is mediated in part by Ag-specific efferent CD8(+) T regulatory (Tr) cells. This model of tolerance is called a.c.-associated immune deviation. The generation of the efferent CD8(+) Tr cell in a.c.-associated immune deviation is dependent on IL-10-producing, CD1d-restricted, invariant Valpha14(+) NKT (iNKT) cells. The iNKT cell subpopulations are either CD4(+) or CD4(-)CD8(-) double negative. This report identifies the subpopulation of iNKT cells that is important for induction of the efferent Tr cell. Because MHC class II(-/-) (class II(-/-)) mice generate efferent Tr cells following a.c. inoculation, we conclude that conventional CD4(+) T cells are not needed for the development of efferent CD8(+) T cells. Furthermore, Ab depletion of CD4(+) cells in both wild-type mice (remove both conventional and CD4(+) NKT cells) and class II(-/-) mice (remove CD4(+) NKT cells) abrogated the generation of Tr cells. We conclude that CD4(+) NKT cells, but not the class II molecule or conventional CD4(+) T cells, are required for generation of efferent CD8(+) Tr cells following Ag introduction into the eye. Understanding the mechanisms that lead to the generation of efferent CD8(+) Tr cells may lead to novel immunotherapy for immune inflammatory diseases.
authors.affiliation: Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Nakamura
authors.forename: Koh-Hei
authors.initials: KH
authors.lastname: Sonoda
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Faunce
authors.forename: Jenny
authors.initials: J
authors.lastname: Gumperz
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamura
authors.forename: Sachiko
authors.initials: S
authors.lastname: Miyake
authors.forename: Joan
authors.initials: J
authors.lastname: Stein-Streilein
mesh_terms: D000818:Animals; D000867:Anterior Chamber / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D005260:Female; D006131:Growth Inhibitors / Q000008:administration & dosage; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007267:Injections; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D006131:Growth Inhibitors; D000949:Histocompatibility Antigens Class II; D010047:Ovalbumin