GLUCOCORTICOIDS ACCELERATE ANTI-T CELL RECEPTOR-INDUCED T-CELL GROWTH

To study steroid regulation of cell-mediated immunity, we used anti-TC R-stimulated rat splenic lymphocyte mitogenesis as our experimental pa radigm. Surprisingly, we found that the principal glucocorticoid of th e rat, corticosterone (CORT), potently enhanced anti-TCR-induced lymph ocyte proliferation after 2 to 3 days in culture, followed by inhibite d cell growth after 5 to 7 days. Thus, glucocorticoids appeared to acc elerate anti-TCR-induced lymphocyte mitogenesis. This effect occurred at physiologic concentrations (50-1000 nM), which are known to be rele ased in vivo after an immune challenge. Kinetic experiments showed tha t CORT had to be present within 60 min after the initiation of TCR act ivation to produce maximal enhancing effects; a delay of 2 h or more l eft CORT ineffective. The lymphocytes incubated with CORT may have an increased sensitivity to IL-2 because 1) CORT suppressed IL-2 producti on throughout the culture period, and 2) an anti-IL-2R mAb completely blocked both control and CORT-treated anti-TCR-induced lymphocyte prol iferation. Although the IL-2R alpha- and beta-chain mRNA concentration s were not altered in CORT-treated splenocyte cultures, we observed by FAGS analysis an increased expression of the IL-2R alpha-chain on COR T-treated TCR alpha beta(+) and CD4(+) T cells after 48 to 72 h of cul ture, suggesting an increased sensitivity of these T cells to IL-2 dur ing the phase of enhanced proliferation. These results demonstrate a c lear distinction between the enhancing effects of glucocorticoids on a nti-TCR-induced lymphocyte proliferation and their well known inhibito ry actions. Thus, the present study expands the regulatory role of glu cocorticoids in cellular immunity, adding a novel effective stimulator y component to their inhibitory properties.