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 th e PL/J mouse is a monophasic disease. We isolated mononuclear cells (M NC) from the central nervous system (CNS), lymph node (LN), blood, and spleen over the course of EAE and counted the number of cells secreti ng 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 a t disease peak and at recovery. A profound transient drop in IL-2 secr eting cells also occurred in LN, blood, and spleen at disease peak and during recovery. IFN-gamma secreting cell number decreased in all com partments as disease evolved. In contrast, IL-4 secreting cell number was greatest in the CNS at disease peak, i.e. IL-4 secreting cells ros e as IL-2 and IFN-gamma secreting cells fell. IL-4 secreting cell numb er 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 MN C did proliferate in response to anti-CD3 mAb at disease peak and this proliferation was augmented by exogenous IL-2. After prolonged cultur e, proliferative response of CNS MNC to anti-CD3 mAb was restored. The se results indicate that during monophasic EAE global suppression of n aive T cell and Th1 T cell cytokine synthesis occurs but that T cell p roliferative responsiveness is selectively inhibited in the CNS. (C) 1 996 Academic Press Limited