J Neurosci Res 2003 Jan 1;71(1):89-103
Matejuk A, Buenafe AC, Dwyer J, Ito A, Silverman M, Zamora A, Subramanian S, Vandenbark AA, Offner H.
Department of Neurology, Oregon Health and Science University, Portland, Oregon.
To investigate regulatory mechanisms which naturally prevent autoimmune diseases, we adopted the genetically restricted immunodeficient (RAG-1(-/-)) 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.