TESTOSTERONE THERAPY AMELIORATES EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AND INDUCES A T-HELPER-2 BIAS IN THE AUTOANTIGEN-SPECIFIC T-LYMPHOCYTE RESPONSE

Female SJL mice are more susceptible than male mice to experimental au toimmune encephalomyelitis (EAE) induced by myelin basic protein (MBP) -specific T lymphocytes. In the present study, we examined mechanisms involved in this gender-related difference in disease susceptibility. MBP-specific T lymphocytes derived from spleens of males during the ef fector phase of adoptive EAE produced significantly higher levels of I L-10, an anti-inflammatory cytokine in EAE. A protective effect of tes tosterone was then shown. Females implanted with dihydrotestosterone p ellets demonstrated a significantly less severe course of EAE as compa red with females implanted with placebo pellets. Finally, MBP-specific T lymphocytes derived from dihydrotestosterone-implanted females prod uced significantly higher levels of IL-10 than those from placebo. Tog ether these data indicate that testosterone exerts a protective effect in EAE that is mediated at least in part by enhanced production of IL -10 by autoantigen-specific T lymphocytes.