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.
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.
Higuchi
M
M
Faculty of Medicine, Kyushu University, Fukuoka, 812-82, Japan.
Nagasawa
K
K
Horiuchi
T
T
Oike
M
M
Ito
Y
Y
Yasukawa
M
M
Niho
Y
Y
D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D015490:HTLV-I Infections / Q000276:immunology*; D015368:Human T-lymphotropic virus 1; D006801:Humans; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology*
D014409:Tumor Necrosis Factor-alpha