PRODUCTION OF A FACTOR, OR FACTORS, SUPPRESSING IL-2 PRODUCTION AND T CELL PROLIFERATION BY SERTOLI CELL-ENRICHED PREPARATIONS

A POTENTIAL ROLE FOR ISLET TRANSPLANTATION IN AN IMMUNOLOGICALLY PRIVILEGED SITE

Abstract

Isolated islet allografts survive indefinitely in the abdominal testis of nonimmunosuppressed diabetic rats. The predominant feature of these testes is that the presence of Sertoli cells, but not Leydig cells, is required for extended survival of the islet allografts. Sertoli cells cultures were therefore established in vitro and we examined the effects of the conditioned media on Con A-stimulated spleen lymphocyte proliferation. These studies revealed that a product(s) secreted by Sertoli cells inhibits Con A—stimulated lymphocyte proliferation in a dose-dependent manner. The synthesis of this product is both temperature-dependent, occurring predominantly at 37°C, and hormone-dependent, requiring the presence of follicle stimulating hormone, in the culture medium. We further examined the mechanism of inhibition of lymphocyte proliferation and showed that Sertoli cell—enriched media inhibit the production of IL-2 in a dose-dependent manner. Furthermore, the finding that the addition of exogenous IL-2 is not able to reverse this inhibition indicates that the Sertoli cell—enriched media inhibit both IL-2 production and IL-2 responsiveness of T lymphocytes.