Enhancement of a human antibody response in vitro mediated by interaction of interferon-α with T lymphocytes

This study describes the effects of human recombinant IFN-α₂ on antibody production in vitro. Whereas the inclusion of IFN-α₂ 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 thet 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-α₂ 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-α₂ 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.