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

Takahiko Nakamura, Kohei Sonoda, Douglas E. Faunce, Jenny Gumperz, Takashi Yamamura, Sachiko Miyake, Joan Stein-Streilein

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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 Vα14+ 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.

Original languageEnglish
Pages (from-to)1266-1271
Number of pages6
JournalJournal of Immunology
Volume171
Issue number3
DOIs
Publication statusPublished - Aug 1 2003

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Natural Killer T-Cells
Regulatory T-Lymphocytes
T-Lymphocytes
Antigens
Anterior Chamber
Immune System Diseases
Interleukin-10
Immunotherapy

All Science Journal Classification (ASJC) codes

  • Immunology

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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. / Nakamura, Takahiko; Sonoda, Kohei; Faunce, Douglas E.; Gumperz, Jenny; Yamamura, Takashi; Miyake, Sachiko; Stein-Streilein, Joan.

In: Journal of Immunology, Vol. 171, No. 3, 01.08.2003, p. 1266-1271.

Research output: Contribution to journalArticle

Nakamura, Takahiko ; Sonoda, Kohei ; Faunce, Douglas E. ; Gumperz, Jenny ; Yamamura, Takashi ; Miyake, Sachiko ; Stein-Streilein, Joan. / 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. In: Journal of Immunology. 2003 ; Vol. 171, No. 3. pp. 1266-1271.
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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 Vα14+ 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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