Intra-CNS activation by antigen-specific T lymphocytes in experimental autoimmune encephalomyelitis

Identification and quantitation of autoreactive T lymphocytes is crucial in order to understand the pathogenesis of autoimmune diseases. we used flow cytometry to analyze autoantigen-specific T cellular responses in the well characterized rat experimental autoimmune encephalomyelitis (EAE) model. Ce lts isolated from both the central nervous system (CNS) tissue and peripher al lymph nodes were analyzed directly ex vivo or after short term in vitro culture with specific autoantigen. CNS infiltrating T lymphocytes displayin g an interferon-gamma response to selected encephalitogenic myelin protein epitopes were measured kinetically during an individual disease episode and also between relapses in a chronic mt EAE model. One of the EAE models use d displays a restriction towards TCRBV8S2 chain usage by the encephalitogen ic T cells. In this model, in vitro production of intracellular interferon- gamma was selectively detected within this T cell subset derived from both the CNS and peripheal lymph nodes. Furthermore, antigen-specific cells infi ltrating the CNS in this model produced several-fold higher amounts of inte rferon-gamma upon antigen stimulation and displayed a significantly increas ed in vivo proliferation compared with peripheral lymphocytes. These data t hus directly demonstrates that T cells stimulated by a specific autoantigen in the periphery primarily acquire effector functions in the cellular envi ronment of the target organ of the autoantigen. (C) 2001 Elsevier Science E X All rights reserved.