Endogenous CD4+BV8S2- T Cells From TG BV8S2+ Donors Confer Complete Protection Against Spontaneous Experimental Encephalomyelitis (Sp-EAE) in TCR Transgenic, RAG super(-/-) Mice

• Published in: Journal of neuroscience research 2003-01, Vol.71 (1), p.89-103
• Main Authors: Matejuk, A, Buenafe, A C, Dwyer, J, Ito, A, Silverman, M, Zamora, A, Subramanian, S, Vandenbark, A A, Offner, H
• Format: Article
• Language: English
• ISSN: 0360-4012
• DOI: 10.1002/jnr.10450

To investigate regulatory mechanisms which naturally prevent autoimmune diseases, we adopted the genetically restricted immunodeficient (RAG-1 super(-/-)) myelin basic protein (MBP)-specific T cell receptor (TCR) double transgenic (T/R-) mouse model of spontaneous experimental autoimmune encephalomyelitis (Sp-EAE). Sp-EAE can be prevented after transfer of CD4+splenocytes from naive immunocompetent mice. RAG-1+ double transgenic (T/R+) mice do not develop Sp-EAE due to the presence of a very small population (about 2%) of non-Tg TCR specificities. In this study, CD4+BV8S2+ T cells that predominate in T/R+ mice, and three additional populations, CD4+BV8S2-, CD4-CD8-BV8S2+, and CD4-CD8+BV8S2+ T cells that expanded in T/R+ mice after immunization with MBP-Ac1-11 peptide, were studied for their ability to prevent Sp-EAE in T/R- mice. Only the CD4+BV8S2- T cell population conferred complete protection against Sp-EAE, similar to unfractionated splenocytes from non-Tg donors, whereas CD4-CD8-BV8S2+ and CD4-BV8S2+ T cells conferred partial protection. In contrast, CD4-CD8+BV8S2+ T cells had no significant protective effects. The highly protective CD4+BV8S2- subpopulation was CD25+, contained non-clonotypic T cells, and uniquely expressed the CCR4 chemokine receptor. Protected recipient T/R- mice had marked increases in CD4+CD25+ Treg-like cells, retention of the pathogenic T cell phenotype in the spleen, and markedly reduced inflammation in CNS tissue. Partially protective CD4+BV8S2+ and CD4- CD8-BV8S2+ subpopulations appeared to be mainly clonotypic T cells with altered functional properties. These three Sp-EAE protective T cell subpopulations possessed distinctive properties and induced a variety of effects in T/R- recipients, thus implicating differing mechanisms of protection.