Gammadelta T-cell Clones From Intestinal Intraepithelial Lymphocytes Inhibit Development of CTL Responses Ex Vivo

Immunology. 2004 Feb;111(2):155-64. doi: 10.1111/j.0019-2805.2003.01793.x.

Abstract

Oral administration of antigen induces a state of tolerance that is associated with activation of CD8+ T cells that can transfer unresponsiveness to naïve syngeneic hosts. These T cells are not lytic, but they inhibit development of antibody, CD4+ T helper cell, and CD8+ cytotoxic T lymphocyte (CTL) responses upon adoptive transfer into naïve, syngeneic mice. In addition, we have shown that depletion of gammadelta T cells by injection of the anti-delta chain antibody (GL3) down modulates the expression of gammadelta T-cell receptor (TCR) and inhibits the induction of oral tolerance to ovalbumin. Oral administration of antigen also fails to induce tolerance in TCR delta-chain knockout mice suggesting that gammadelta T cells play a critical, active role in tolerance induced by orally administered antigen. To further study the contribution of gammadelta T cells to tolerance, murine gammadelta T cells were isolated from intraepithelial lymphocytes (IEL) of the small intestine by stimulation with splenic filler cells, concanavalin A and growth factors. gammadelta IEL lines demonstrated lytic activity in a redirected lysis assay. gammadelta T-cell clones express different gammadelta TCR genes and secrete large amounts of interleukin (IL)-10, but little or no IL-2, IL-4, or interferon-gamma. gammadelta IEL clones expressed transforming growth factor-beta1 and macrophage migration inhibitory factor, as well as IL-10, mRNA. Moreover, gammadelta T-cell clones potently inhibited the generation of CTL responses by secreted molecules rather than by direct cell-to-cell contact.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • Clone Cells / immunology
  • Cytotoxicity, Immunologic / immunology
  • Epithelial Cells / immunology
  • Immune Tolerance
  • Immunity, Mucosal
  • Immunophenotyping
  • Intestinal Mucosa / immunology*
  • Intestine, Small / immunology*
  • Lymphocyte Culture Test, Mixed
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred Strains
  • Receptors, Antigen, T-Cell, alpha-beta / analysis
  • Receptors, Antigen, T-Cell, gamma-delta / analysis*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta