Differential Effects of Human Alpha and Gamma Interferons on Mixed Lymphocyte Culture and on T-Cell-Mediated Cytotoxicity

Abstract
We compared the effects of natural and recombinant (r) alpha (IFN-α) and gamma (IFN-γ) interferons on the proliferative responses of human peripheral blood mononuclear cells to mitogens and allogeneic cells in mixed lymphocyte culture (MLC) and on the generation of specific T-cell-mediated cytotoxicity. In 14 of 19 donors, natural IFN-γ and rIFN-γ had no significant effect on the proliferative responses to mitogens or allogeneic cells in MLC, even at very high IFN-γ concentrations (10,000 U/ml). In the remaining 5 donors, a statistically significant (p 2 significantly inhibited (p 2. Additionally, we compared the ability of human rIFN-α subtypes to inhibit proliferative responses to allogeneic cells in MLC. rIFN-α2, rIFN-α4, and rIFNα7 displayed the most potent inhibitory activity of allogeneic responses and were active at concentrations as low as 0.3–0.6 ng/ml. The rIFN-α21 hybrid molecule was also capable of significantly inhibiting proliferative responses in MLC at concentrations of 0.6 ng/ml or higher. rIFN-α1 and rIFN-δ4α1 inhibited at considerably higher concentrations (30 ng/ml or higher).

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