Hofstetter, H. H., O. S. Targoni, A. Y. Karulin, T. G. Forsthuber, M. Tary-Lehmann, and P. V. Lehmann. 2005. Does the frequency and avidity spectrum of the neuroantigen-specific T cells in the blood mirror the autoimmune process in the central nervous system of mice undergoing experimental allergic encephalomyelitis? J. Immunol. 174:4598.

Categories: Autoimmunity, Functional T cell avidity, Single-cell resolution

Keywords: Acute Disease / Animals / Autoantigens / Autoimmunity / Central Nervous System / immunology / Chronic Disease / Encephalomyelitis,Autoimmune,Experimental / blood / Female / Humans / Interferon Type II / biosynthesis / Lymph Nodes / Male / Mice / Myelin Basic Proteins / Peptide Fragments / Research Support,Non-U.S.Gov't / Research Support,U.S.Gov't,P.H.S. / Spleen / T-Lymphocyte Subsets / Time Factors

Abstract: In humans, studies of autoreactive T cells that mediate multiple sclerosis have been largely confined to testing peripheral blood lymphocytes. Little is known how such measurements reflect the disease-mediating autoreactive T cells in the CNS. This information is also not available for murine experimental allergic encephalomyelitis (EAE); the low number of T cells that can be obtained from the blood or the brain of mice prevented such comparisons. We used single-cell resolution IFN-gamma ELISPOT assays to measure the frequencies and functional avidities of myelin basic protein (MBP:87-99)-specific CD4 cells in SJL mice immunized with this peptide. Functional MBP:87-99-specific IFN-gamma-producing cells were present in the CNS during clinical signs of EAE, but not during phases of recovery. In contrast, MBP:87-99-specific T cells persisted in the blood during all stages of the disease, and were also present in mice that did not develop EAE. Therefore, the increased frequency of MBP:87-99-reactive T cells in the blood reliably reflected the primed state, but not the inflammatory activity of these cells in the brain. The functional avidity of the MBP:87-99-reactive T cells was identical in the brain and blood and did not change over 2 mo as the mice progressed from acute to chronic EAE. Therefore, high-affinity T cells did not become selectively enriched in the target organ, and avidity maturation of the MBP:87-99-specific T cell repertoire did not occur in the observation period. The data may help the interpretation of measurements made with peripheral blood lymphocytes of multiple sclerosis patients.