Preferential distribution of V beta 8.2-positive T cells in the central nervous system of rats with myelin basic protein-induced autoimmune encephalomyelitis.Eur J Immunol. 1993 Oct; 23(10):2399-406.EJ
To determine the role of encephalitogenic T cells in the formation of lesions in the central nervous system (CNS), experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats by immunization with either myelin basic protein (MBP) or the synthetic peptide which corresponds to the 87-100 sequence of guinea pig MBP, and T cells expressing T cell receptor (TcR) V beta 8.2, V beta 8.5, V beta 10 and V beta 16 in the lymphoid organs and CNS were localized and quantified by flow cytometry (FCM) and immunohistochemistry. In normal rats, the percentage of T cells expressing these V beta phenotypes to the total number of TcR alpha beta+ T cells, as determined by FCM, ranged from 5% to 10% in the lymph node. V beta 16+ T cells were the most predominant population among the four V beta subsets tested. Essentially the same findings were obtained from the analysis of the lymphoid organs of rats with EAE which had been induced by immunization with the same two antigens. In sharp contrast, 15-20% of the T cells isolated from lesions of MBP-induced EAE expressed V beta 8.2. Thus, the percentage of V beta 8.2+ T cells in the EAE lesions was threefold higher than that in the lymph node, while the proportions of V beta 8.5+, V beta 10+ and V beta 16+ T cells were about the same in both organs. The predominance of V beta 8.2+ T cells in EAE lesions was confirmed by counts of immunohistochemically stained T cells in the spinal cord. Moreover, it was revealed that (i) the predominance of V beta 8.2+ T cells was greatest during the development of EAE and became less obvious at the recovery state, and (ii) at the peak stage of EAE, approximately 85% of V beta 8.2+ T cells were distributed in the parenchyma while 15% were in the perivascular space of the CNS vessels. These findings indicate that encephalitogenic T cells which express V beta 8.2 infiltrate the CNS at a very early stage of EAE and become the predominant population in infiltrating T cells, and further suggest that encephalitogenic T cells, not only recruit inflammatory cells in the CNS, but also cause neural tissue damage, such as demyelination.