Differential responses of invariant V alpha 24J alpha Q T cells and MHC class II-restricted CD4+ T cells to dexamethasone

J Immunol. 1999 Sep 1;163(5):2522-9.

Abstract

NK T cells are a T cell subset in the human that express an invariant alpha-chain (V alpha 24invt T cells). Because of the well-described immunomodulation by glucocorticoids on activation-induced cell death (AICD), the effects of dexamethasone and anti-CD3 stimulation on V alpha 24invt T cell clones and CD4+ T cell clones were investigated. Dexamethasone significantly enhanced anti-CD3-mediated proliferation of V alpha 24invt T cells, whereas CD4+ T cells were inhibited. Addition of neutralizing IL-2 Ab partially abrogated dexamethasone-induced potentiation of V alpha 24invt T cell proliferation, indicating a role for autocrine IL-2 production in corticosteroid-mediated proliferative augmentation. Dexamethasone treatment of anti-CD3-stimulated V alpha 24invt T cells did not synergize with anti-Fas blockade in enhancing proliferation or preventing AICD. The V alpha 24invt T cell response to dexamethasone was dependent on the TCR signal strength. In the presence of dexamethasone, lower doses of anti-CD3 inhibited proliferation of V alpha 24invt T cells and CD4+ T cells; at higher doses of anti-CD3, which caused inhibition of CD4+ T cells, the V alpha 24invt T cell clones proliferated and were rescued from AICD. These results demonstrate significant differences in TCR signal strength required between V alpha 24invt T cells and CD4+ cells, and suggest important immunomodulatory consequences for endogenous and exogenous corticosteroids in immune responses.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Antibodies, Blocking / pharmacology
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD1 / immunology
  • Antigens, CD1d
  • Antigens, Differentiation, B-Lymphocyte / metabolism*
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Autocrine Communication / drug effects
  • Autocrine Communication / immunology
  • CD3 Complex / immunology
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Clone Cells
  • Dexamethasone / pharmacology*
  • Dose-Response Relationship, Immunologic
  • Histocompatibility Antigens Class II / immunology*
  • Histocompatibility Antigens Class II / metabolism*
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Interleukin-2 / metabolism
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • fas Receptor / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Antigens, CD1
  • Antigens, CD1d
  • Antigens, Differentiation, B-Lymphocyte
  • CD1D protein, human
  • CD3 Complex
  • Histocompatibility Antigens Class II
  • Immunosuppressive Agents
  • Interleukin-2
  • Receptors, Antigen, T-Cell, alpha-beta
  • fas Receptor
  • invariant chain
  • Dexamethasone