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The Journal of Immunology, 2003, 171: 1266-1271.
Copyright © 2003 by The American Association of Immunologists

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 Site1

Takahiko Nakamura*, Koh-Hei Sonoda2,*, Douglas E. Faunce3,*, Jenny Gumperz{dagger}, Takashi Yamamura§, Sachiko Miyake§ and Joan Stein-Streilein4,*,{ddagger}

* Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114; Divisions of {dagger} Rheumatology, Immunology, and Allergy, and {ddagger} Pulmonary and Critical Care, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115; and § Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan

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 V{alpha}14+ 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.




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