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

Masanori Higuchi, Kohei Nagasawa, Takahiko Horiuchi, Masahiro Oike, Yushi Ito, Masaki Yasukawa, Yoshiyuki Niho

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Abstract

The 26-kDa membrane tumor necrosis factor-α (TNF-α) 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-α. 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-α antibody (Ab). IgG synthesis was not stimulated, however, probably because of lack of CD40 ligand expression on the infected T cells. Anti-TNF-α Ab treatment stimulated the secretion of interleukin (IL)-2 and interferon gamma (IFN-γ) in the infected T cells. These effects were not induced by anti-TNF receptor Ab treatment. Anti-TNF-α Ab also induced the elevation of intracellular calcium concentration in the infected T cells. These results suggest that T cells expressing membrane TNF-α can be directly stimulated through this molecule. Thus, it is suggested that the 26-kDa membrane TNF-α 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-α on their surface.

Original languageEnglish
Pages (from-to)133-140
Number of pages8
JournalClinical Immunology and Immunopathology
Volume82
Issue number2
DOIs
Publication statusPublished - Feb 1997

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Immunology

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