Retinoic acid promotes proliferation and induces expression of retinoic acid receptor-α gene in murine T lymphocytes

We have studied the direct effect of retinoic acid on the antigen-specific proliferative response of a T lymphocyte clone and have investigated the related expression of the retinoic acid receptor-α gene (RAR-α). Retinoic acid provided direct growth support, in a dose-dependent manner, for hen egg white lysozyme (HEL)-activated T lymphocytes in serum-free medium. The increase of T lymphocyte proliferation supported by retinoic acid was dose dependent, and best effects were achieved at physiological concentrations (10^-9-10^-7 mol/liter). Expression of RAR-α mRNA in antigen-stimulated T lymphocyte cultures was upregulated by retinoic acid in a dose-dependent manner; maximal expression occurred within 6 hr of culture and in response to 10^-9-10^-7 mol/liter retinoic acid. Lower expression of RAR-α was attained by antigen or mitogen (concanavalin A) in the absence of externally added retinoic acid. The inclusion of retinoic acid at the time of HEL processing led to increased T lymphocyte proliferation, provided antigen presenting cell cultures had been maintained for 16 hr. Our results indicate that retinoic acid and RAR-α might function in T lymphocytes in a manner similar to that described in other cell systems, namely as ligand-inducible transcriptional enhancer factors.