Control of T cell reactivation by regulatory Qa-1-restricted CD8+ T cells

J Immunol. 2010 Jun 15;184(12):6585-91. doi: 10.4049/jimmunol.0903109. Epub 2010 May 19.

Abstract

Administration of attenuated pathogenic T cell clones, a procedure known as T cell vaccination, induces CD8+ T cells specific for peptides derived from the Vbeta-chain of the TCR presented by the MHC class Ib molecule, Qa-1 expressed on the vaccine cells. These regulatory CD8+ T cells have the capacity to control the activation of endogenous T cells expressing the same TCR Vbeta-chain as the vaccinating cells. We hypothesized that vaccination with NKT cells could also induce Qa-1-restricted CD8+ T cells that would control NKT cell activation. We tested this hypothesis in a murine model of Con A-induced hepatitis that is induced by NKT cells. Vaccination with NKT cells effectively induced protective Qa-1-restricted CD8+ T cells that prevented hepatitis. Surprisingly, upon vaccination with T cells expressing Vbeta-chains irrelevant to NKT cells, we discovered that the specificity of vaccine-induced Qa-1-restricted CD8+ T cells was not limited to the Vbeta-chain of the vaccinating cells. We further show that these regulatory Qa-1-restricted CD8+ T cells arise spontaneously upon polyclonal activation of T cells in the absence of deliberate T cell vaccination. These experiments provide new insight into a CD8+ T cell compartment that regulates the immediate reactivation of conventional T cells and NKT cells.

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Separation
  • Concanavalin A / immunology
  • Concanavalin A / toxicity
  • Flow Cytometry
  • Hepatitis / immunology
  • Histocompatibility Antigens Class I / immunology
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Mitogens / immunology
  • Mitogens / toxicity
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / transplantation
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocyte Subsets / immunology*
  • Vaccination

Substances

  • Histocompatibility Antigens Class I
  • Mitogens
  • Q surface antigens
  • Receptors, Antigen, T-Cell
  • Concanavalin A