| 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<0.00l) enhancement by 49 ± 8% of the proliferative responses was observed. In contrast, natural IFN-α and rIFN-α<inf>2</inf> significantly inhibited (p<0.00l) 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-α 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-γ did not affect the generation of specific cytotoxicity in MLC, although it was significantly enhanced by natural IFN-α and rIFN-α<inf>2</inf>. Additionally, we compared the ability of human rIFN-α subtypes to inhibit proliferative responses to allogeneic cells in MLC. rIFN-a<inf>2</inf>, rIFN-α<inf>4</inf>, and rIFN-α<inf>7</inf> displayed the most potent inhibitory activity of allogeneic esponses and were active at concentrations as low as 0.3-0.6 ng/ml. The rIFN-α<inf>2</inf>/α<inf>1</inf> hybrid molecule was also capable of significantly inhibiting proliferative responses in MLC at concentrations of 0.6 ng/ml or higher. rIFN-α<inf>1</inf> and rIFN-δ<inf>4</inf>α<inf>1</inf> inhibited at considerably higher concentrations (30 ng/ml or higher). © 1988 S. Karger AG, Basel. |
| Keywords: |
human cell; alpha interferon; comparative study; lymphocyte proliferation; t-lymphocytes; cell division; interleukin 2; mixed lymphocyte culture; lymphocyte culture test, mixed; gamma interferon; cell culture; recombinant proteins; cytotoxicity, immunologic; normal human; interleukin-2; cell mediated cytotoxicity; interferon type i; interferon type ii; alpha interferon derivative; human; priority journal; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; depression, chemical
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