Effect of interferon-gamma on myelin basic protein-specific T cell line proliferation in response to antigen-pulsed accessory cells

Cell Immunol. 1992 Dec;145(2):311-23. doi: 10.1016/0008-8749(92)90334-l.

Abstract

We have shown previously that treatment of SJL/J mice with anti-interferon-gamma monoclonal antibody (mAb) exacerbated experimental allergic encephalomyelitis (EAE) only if administered at the time of encephalitogenic challenge. Here we investigate the role of interferon-gamma (IFN-gamma) and anti-IFN-gamma mAb in the early events of T cell activation in vitro. Pretreatment of murine peritoneal exudate cells (PEC) with IFN-gamma led to a significant increase in their ability to activate myelin basic protein (MBP)-specific, short-term T cell lines. When exogenous IFN-gamma was added to cocultures of T cells and MBP-pulsed PEC, the antigen-specific T cell proliferation was considerably reduced. Anti-IFN-gamma mAb added to these cultures neutralized the inhibitory effect of the exogenous IFN-gamma on T cell proliferation but had no visible effect on class II MHC expression by the antigen-pulsed PEC present in the same cultures. A reduction in T cell proliferation was also observed when the T cells were treated with IFN-gamma prior to coculture with the MBP-pulsed PEC. These results demonstrate that, on one hand, IFN-gamma enhances the ability of PEC to induce antigen-specific T cell proliferation but, on the other hand, acts on the T cells themselves by inhibiting their proliferation in response to the antigen-pulsed PEC. This may explain why treatment with anti-IFN-gamma antibody in vivo induces EAE exacerbation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigen-Presenting Cells / physiology*
  • Antigens / immunology*
  • Cell Line
  • Female
  • Guinea Pigs
  • Interferon-gamma / pharmacology
  • Interferon-gamma / physiology*
  • Lymphocyte Activation / drug effects*
  • Mice
  • Myelin Basic Protein / immunology*
  • Rats
  • Recombinant Proteins
  • T-Lymphocytes / immunology*

Substances

  • Antibodies, Monoclonal
  • Antigens
  • Myelin Basic Protein
  • Recombinant Proteins
  • Interferon-gamma