Suppressor cell induction factor: a new mediator released by stimulated human lymphocytes and distinct from previously described lymphokines.

Suppressor cell induction factor (SIF) was produced by alloantigen-stimulated human peripheral blood lymphocytes, and it activated human T cells to become effective suppressors of the mixed lymphocyte reaction (MLR). The activity of SIF was resistant to 56 degrees C and to pH 2, and was precipitated by 50 to 80% saturated ammonium sulfate. SIF had a m.w. range, as determined by gel filtration, of 18,000 to 29,000; it did not bind to DEAE cellulose columns; and it was recovered in the pH range from 6.9 to 7.3 on isoelectric focusing. SIF was biochemically separable from IL 2, BF, IFN-gamma, and CSF. Furthermore, IL 2 activity was completely removed by absorption of MLC supernatants by murine cytotoxic T lymphocyte line (CTLL) cells, whereas SIF activity was unabsorbable, thus distinguishing SIF from IL 2. In addition, antiviral activity of MLC supernatants was completely abolished by anti-human IFN-gamma serum, whereas SIF activity was unaffected by this antiserum, thus distinguishing SIF from IFN-gamma. Since treatment of these supernatants with antiserum against human lymphoblastoid cell IFN(alpha/beta) had no effect on either antiviral or SIF activities in these supernatants, SIF was also distinguishable from IFN alpha/beta. These results indicate that SIF is a distinct new lymphokine with the ability to induce suppressor function in human T cells.