Enhancement of a human antibody response in vitro mediated by interaction of interferon-alpha with T lymphocytes.
This study describes the effects of human recombinant IFN-alpha 2 on antibody production in vitro. Whereas the inclusion of IFN-alpha 2 in cultures for 7 days had a relatively minor effect on pokeweed mitogen (PWM)-induced antibody production, it resulted in a dose-related enhancement of a hapten-specific primary antibody response. Comparison of PWM and IFN-induced [3H]thymidine uptake indicated that the observed IFN activation was not polyclonal. Pretreatment of T cells with IFN for 1 hr before recombination with untreated autologous B lymphocytes increased the anti-TNP response four-fold, whereas similar pretreatment of B lymphocytes had no effect. Furthermore, 2000 R x-irradiation of T cells before coculture with autologous B lymphocytes and IFN abrogated the TNP-specific response. These results indicate that IFN modulates TNP-specific antibody production via a radiosensitive T-helper function. Further subfractionation by panning suggests that the enhancement is mediated by the Leu-3a+ helper/inducer T cell subset. Evidence that a 1-hr exposure to IFN was sufficient to modulate antibody production prompted the examination of T cells for possible receptor mechanisms. Scatchard analysis of 125I-IFN-alpha 2 binding revealed approximately 65 high affinity IFN receptors per cell with an apparent dissociation constant (Kd) of 4.4 X 10(-10) M. This paper is the first demonstration of the role of T cells in mediating the effects of recombinant IFN-alpha 2 on human primary antibody responses in vitro. These data further suggest that the observed modulation of hapten-specific antibody production in vitro by IFN may involve the binding of IFN to specific cellular receptors expressed by T lymphocytes.
D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008211:Lymphocyte Cooperation / Q000187:drug effects* / Q000528:radiation effects; D011043:Pokeweed Mitogens / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000145:classification; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects
D007370:Interferon Type I; D011043:Pokeweed Mitogens; D011994:Recombinant Proteins