Differential effects of human alpha and gamma interferon on mixed lymphocyte culture and on T-cell-mediated cytotoxicity. Inhibition of proliferation but not of IL-2 production by alpha interferons.
We compared the effects of natural and recombinant (r) alpha (IFN-alpha) and gamma (IFN-gamma) 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-gamma and rIFN-gamma had no significant effect on the proliferative responses to mitogens or allogeneic cells in MLC, even at very high IFN-gamma concentrations (10,000 U/ml). In the remaining 5 donors, a statistically significant (p less than 0.001) enhancement by 49 +/- 8% of the proliferative responses was observed. In contrast, natural IFN-alpha and rIFN-alpha 2 significantly inhibited (p less than 0.001) proliferative responses to mitogens and to allogeneic cells, even at concentrations as low as 10 U/ml, in agreement with previous reports. Although natural and recombinant IFN-alpha significantly inhibited these proliferative responses, they did not affect interleukin-2 (IL-2) production in these cultures, suggesting that they inhibit proliferation by a mechanism that does not involve inhibition of IL-2 production. rIFN-gamma did not affect the generation of specific cytotoxicity in MLC, although it was significantly enhanced by natural IFN-alpha and rIFN-alpha 2. Additionally, we compared the ability of human rIFN-alpha subtypes to inhibit proliferative responses to allogeneic cells in MLC. rIFN-alpha 2, rIFN-alpha 4, and rIFN alpha 7 displayed the most potent inhibitory activity of allogeneic responses and were active at concentrations as low as 0.3-0.6 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
Chae
F
F
Memorial Sloan-Kettering Cancer Center, New York, N.Y.
Oleszak
E
E
Fox
F E
FE
Trotta
P
P
Mele
C A
CA
Hawrylko
E
E
Platsoucas
C D
CD
D002455:Cell Division / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003864:Depression, Chemical; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D007959:Lymphocyte Culture Test, Mixed; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects
D007370:Interferon Type I; D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma