Role and function of antigen nonspecific suppressor factors

Although antigen-nonspecific suppressor factors described by various investigators appear to exhibit a certain amount of heterogeneity in both physical and biological properties, these proteins also exhibit significant similarities. Nonspecific suppressor factors are generally produced by Ly 2+ (murine) or OKT8+ (human) T lymphocytes. One protein, soluble immune response suppressor (SIRS), is produced by T lymphocytes after incubation with mitogens, interferons, or histamine, and must be activated by peroxides to inhibit cell division or immune function. SIRS appears to inhibit cell division by causing oxidation of a portion of cellular protein sylfhydryls and, in particular, causes a decrease in intracellular levels of deoxyribonucleotide triphosphates. This decrease is readily reversed by sulhydryl reducing agents, such as 2-mercaptoethanol. The activity of SIRS and other suppressor factors is inhibited by growth factors, such as interleukin 2, and the activity of interleukin 2 is inhibited by antigen-nonspecific suppressor factors. Further, SIRS or SIRS-like proteins are produced during various diseases associated with suppressed immune responsiveness including acquired immune deficiency syndrome, schistosomiasis, and nephrotic syndrome. These data suggest that antigen-nonspecific suppressor factors may have an important physiological role in regulating immune responses and cell division in general.