Global inhibition of IL-2 and IFN-gamma secreting T cells precedes recovery from acute monophasic experimental autoimmune encephalomyelitis.
Actively induced experimental autoimmune encephalomyelitis (EAE) in the PL/J mouse is a monophasic disease. We isolated mononuclear cells (MNC) from the central nervous system (CNS), lymph node (LN), blood, and spleen over the course of EAE and counted the number of cells secreting IL-2, IFN-gamma or IL-4 in response to polyclonal stimulation. IL-2 secreting cells were present in the CNS at disease onset but absent at disease peak and at recovery. A profound transient drop in IL-2 secreting cells also occurred in LN, blood, and spleen at disease peak and during recovery. IFN-gamma secreting cell number decreased in all compartments as disease evolved. In contrast, IL-4 secreting cell number was greatest in the CNS at disease peak, i.e. IL-4 secreting cells rose as IL-2 and IFN-gamma secreting cells fell. IL-4 secreting cell number did not change appreciably in LN, blood, and splenic MNC as disease evolved. CNS MNC at disease peak failed to proliferate in response to anti-CD3 mAb but did so in response to IL-2. LN, blood and splenic MNC did proliferate in response to anti-CD3 mAb at disease peak and this proliferation was augmented by exogenous IL-2. After prolonged culture, proliferative response of CNS MNC to anti-CD3 mAb was restored. These results indicate that during monophasic EAE global suppression of naive T cell and Th1 T cell cytokine synthesis occurs but that T cell proliferative responsiveness is selectively inhibited in the CNS.
Jensen
M A
MA
Department of Neurology, University of Chicago, IL 60637, USA.
Arnason
B G
BG
Toscas
A
A
Noronha
A
A
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007376:Interleukin-2; D007371:Interferon-gamma