Inhibition of Follicular T-helper Cells by CD8(+) Regulatory T Cells Is Essential for Self Tolerance

Nature. 2010 Sep 16;467(7313):328-32. doi: 10.1038/nature09370.

Abstract

The ability to produce vigorous immune responses that spare self tissues and organs depends on the elimination of autoreactive T and B cells. However, purging of immature and mature self-reactive T and B cells is incomplete and may also require the involvement of cells programmed to suppress immune responses. Regulatory T cells (T(reg)) belonging to the CD4(+) T-cell subset may have a role in preventing untoward inflammatory responses, but T-cell subsets programmed to inhibit the development of autoantibody formation and systemic-lupus-erythematosus-like disease have not yet been defined. Here we delineate a CD8(+) regulatory T-cell lineage that is essential for the maintenance of self tolerance and prevention of murine autoimmune disease. Genetic disruption of the inhibitory interaction between these CD8(+) T cells and their target Qa-1(+) follicular T-helper cells results in the development of a lethal systemic-lupus-erythematosus-like autoimmune disease. These findings define a sublineage of CD8 T cells programmed to suppress rather than activate immunity that represents an essential regulatory element of the immune response and a guarantor of self tolerance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antibody Affinity / immunology
  • Antigens / immunology
  • Autoantibodies / biosynthesis
  • Autoantibodies / immunology
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Lineage
  • Germinal Center / cytology
  • Germinal Center / immunology
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Hyaluronan Receptors / immunology
  • Hyaluronan Receptors / metabolism
  • Immunoglobulin G / blood
  • Lupus Erythematosus, Systemic / immunology
  • Mice
  • Models, Immunological
  • Mutation
  • Self Tolerance / immunology*
  • T-Lymphocytes, Helper-Inducer / cytology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Antibodies
  • Antigens
  • Autoantibodies
  • Histocompatibility Antigens Class I
  • Hyaluronan Receptors
  • Immunoglobulin G
  • Q surface antigens