Membrane tumor necrosis factor-alpha (TNF-alpha) expressed on HTLV-I-infected T cells mediates a costimulatory signal for B cell activation--characterization of membrane TNF-alpha

Clin Immunol Immunopathol. 1997 Feb;82(2):133-40. doi: 10.1006/clin.1996.4291.

Abstract

The 26-kDa membrane tumor necrosis factor-alpha (TNF-alpha) expressed on activated CD4(+) T cells is a novel candidate for the functional membrane molecule in T-B cell interactions. We found that normal human T cells, when infected with human T cell lymphotropic virus type I (HTLV-I) in vitro, were induced to express the 26-kDa membrane TNF-alpha. The infected T cells, through this molecule, activated autologous B cells to produce immunoglobulin (Ig)M in a contact-dependent manner, which was partially inhibited by anti-TNF-alpha antibody (Ab). IgG synthesis was not stimulated, however, probably because of lack of CD40 ligand expression on the infected T cells. Anti-TNF-alpha Ab treatment stimulated the secretion of interleukin (IL)-2 and interferon gamma (IFN-gamma) in the infected T cells. These effects were not induced by anti-TNF receptor Ab treatment. Anti-TNF-alpha Ab also induced the elevation of intracellular calcium concentration in the infected T cells. These results suggest that T cells expressing membrane TNF-alpha can be directly stimulated through this molecule. Thus, it is suggested that the 26-kDa membrane TNF-alpha on HTLV-I-infected T cells plays a role in polyclonal B cell activation and may be involved in the pathogenesis of some HTLV-I-associated diseases. Additionally, our results suggest a novel mechanism by which cytokine production can be modulated in these T cells through membrane TNF-alpha on their surface.

MeSH terms

  • Antigen Presentation*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / virology
  • Cell Line
  • Cell Membrane / immunology
  • HTLV-I Infections / immunology*
  • Human T-lymphotropic virus 1*
  • Humans
  • Lymphocyte Activation*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / virology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / immunology*

Substances

  • Tumor Necrosis Factor-alpha