ANERGY INDUCTION IN ENCEPHALITOGENIC T-CELLS BY BRAIN MICROVESSEL ENDOTHELIAL-CELLS IS INHIBITED BY INTERLEUKIN-1

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory dis ease of the central nervous system (CNS) which can be induced, in susc eptible strains like Lewis rats, by transfer of activated myelin basic protein (MBP)-specific CD4(+) T lymphocytes. The role of cerebral end othelium in the onset of EAE,with regard to adhesion, activation and i nfiltration in the CNS of encephalitogenic T lymphocytes, is not fully understood. When pretreated by interferon-gamma, the immortalized Lew is rat brain microvessel endothelial (RBE4) cells expressed major hist ocompatibility complex class II molecules and stimulated MBP-specific proliferation and cytolytic activity of the syngeneic encephalitogenic T cell line, designated PAS. However, RBE4-stimulated PAS lymphocytes subsequently entered an unresponsive state, known as anergy When inoc ulated in syngeneic animals, anergic PAS cells, although still cytotox ic, failed to induce EAE, and no cell infiltration was detectable with in CNS. The addition of interleukin-1 beta (IL-1 beta) during MBP pres entation by RBE4 cells prevented T cell anergy induction, and maintain ed T cell encephalitogenicity, although PAS cells stimulated in these conditions caused delayed and attenuated clinical signs of EAE, with o nly discrete inflammatory lesions in the CNS, compared with EAE induce d by PAS cells fully activated by thymic cells. Altogether, our result s indicate that MBP presentation by brain microvessel endothelial cell s to encephalitogenic T cells induces T cell anergy and loss of pathog enicity. In addition, IL-1 beta co-stimulation of T cells prevents ane rgy induction in vitro and at least partially maintains encephalitogen icity in vivo.