Danger and OX40 receptor signaling synergize to enhance memory T cell survival by inhibiting peripheral deletion

J Immunol. 2000 Jan 1;164(1):107-12. doi: 10.4049/jimmunol.164.1.107.

Abstract

This report defines a cell surface receptor (OX40) expressed on effector CD4 T cells, which when engaged in conjunction with a danger signal, rescues Ag-stimulated effector cells from activation-induced cell death in vivo. Specifically, three signals were necessary to promote optimal generation of long-lived CD4 T cell memory in vivo: Ag, a danger signal (LPS), and OX40 engagement. Mice treated with Ag or superantigen (SAg) alone produced very few SAg-specific T cells. OX40 ligation or LPS stimulation, enhanced SAg-driven clonal expansion and the survival of responding T cells. However, when SAg was administered with a danger signal at the time of OX40 ligation, a synergistic effect was observed which led to a 60-fold increase in the number of long-lived, Ag-specific CD4 memory T cells. These data lay the foundation for the provision of increased numbers of memory T cells which should enhance the efficacy of vaccine strategies for infectious diseases, or cancer, while also providing a potential target (OX40) to limit the number of auto-Ag-specific memory T cells in autoimmune disease.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / physiology
  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Survival / immunology
  • Clonal Deletion / immunology*
  • Enterotoxins / pharmacology
  • Epitopes, T-Lymphocyte / immunology
  • Immunologic Memory* / genetics
  • Ligands
  • Lymphocyte Activation
  • Membrane Glycoproteins*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • OX40 Ligand
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor / physiology*
  • Self Tolerance / physiology
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Superantigens / pharmacology
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / biosynthesis
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism*
  • Tumor Necrosis Factors

Substances

  • Adjuvants, Immunologic
  • Enterotoxins
  • Epitopes, T-Lymphocyte
  • Ligands
  • Membrane Glycoproteins
  • OX40 Ligand
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor
  • Superantigens
  • Tnfrsf4 protein, mouse
  • Tnfsf4 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Tumor Necrosis Factors
  • enterotoxin A, Staphylococcal