Anergy induction in encephalitogenic T cells by brain microvessel endothelial cells is inhibited by interleukin-1

Autor: Dominique Bernard, Sandrine Bourdoulous, Christine Le Page, Alfredo J. Zamora, Pierre-Olivier Couraud, Evelyne Beraud, Arnaud Ferry, A. Donny Strosberg
Rok vydání: 1995
Předmět:
Zdroj: European journal of immunology. 25(5)
ISSN: 0014-2980
Popis: Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS) which can be induced, in susceptible strains like Lewis rats, by transfer of activated myelin basic protein (MBP)-specific CD4+ T lymphocytes. The role of cerebral endothelium in the onset of EAE, with regard to adhesion, activation and infiltration in the CNS of encephalitogenic T lymphocytes, is not fully understood. When pretreated by interferon-gamma, the immortalized Lewis rat brain microvessel endothelial (RBE4) cells expressed major histocompatibility 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 inoculated in syngeneic animals, anergic PAS cells, although still cytotoxic, failed to induce EAE, and no cell infiltration was detectable within CNS. The addition of interleukin-1 beta (IL-1 beta) during MBP presentation by RBE4 cells prevented T cell anergy induction, and maintained T cell encephalitogenicity, although PAS cells stimulated in these conditions caused delayed and attenuated clinical signs of EAE, with only discrete inflammatory lesions in the CNS, compared with EAE induced by PAS cells fully activated by thymic cells. Altogether, our results indicate that MBP presentation by brain microvessel endothelial cells to encephalitogenic T cells induces T cell anergy and loss of pathogenicity. In addition, IL-1 beta co-stimulation of T cells prevents anergy induction in vitro and at least partially maintains encephalitogenicity in vivo.
Databáze: OpenAIRE