Suppressive effect of thymosin fraction 5 on proliferation of cultured human T lymphocytes

The effects of thymosin fraction 5 (F5), an extract of bovine thymus containing multiple polypeptides, on the proliferation of cultured T cells (CTC), a continuously proliferating subpopulation of peripheral blood T lymphocytes, stimulated by either phytohemagglutinin (PHA) or delectinated interleukin 2 (IL-2) were studied. Addition of F5 to cultures significantly and consistently inhibited CTC responsiveness to PHA, with the degree of inhibition being greater using a suboptimal concentration of mitogen. F5 did not significantly or consistently inhibit CTC proliferation induced by IL-2. These studies suggest that the suppressive effect of F5 may be primarily mediated by decreased IL-2 production instead of effects on IL-2 activity or efficiency in stimulating CTC proliferation. Since prostaglandins inhibit the proliferation of CTC in response to PHA or IL-2 (R.D. Maca (1983) Immunopharmacology 6:267), studies were undertaken to determine if the observed inhibition was mediated by effects of F5 on prostaglandin E2 (PGE2). The inhibitory effect of F5 on PHA responsiveness of CTC was not affected by the addition of indomethacin indicating that suppression by F5 is not mediated by stimulating the production or release of cyclooxygenase-derived prostaglandins, such as PGE2. Furthermore, PGE2 could not be detected in supernatants of F5-treated CTC stimulated by PHA. When PGE2 was added to F5-treated CTC cultures, the PHA response was inhibited indicating that the suppressive effects of F5 and PGE2 were additive and that F5 did not modulate the sensitivity of CTC to PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)