T-HELPER LYMPHOCYTES SPECIFIC FOR MYELIN BASIC-PROTEIN - LOW-DENSITY ACTIVATION PROLONGS A POSTACTIVATION REFRACTORY PHASE MARKED BY DECREASED PATHOGENICITY AND ENHANCED SENSITIVITY TO ANERGY

Regulation of experimental autoimmune encephalomyelitis (EAE) in Lewis rats may involve activation-dependent negative feedback pathways of T -helper cells, Previous studies have shown that T-helper cells specifi c for myelin basic protein exhibit a postactivation refractory phase d uring which antigenic restimulation elicits proliferation without prod uction of IL-2, Herein, we show that postactivation refractoriness inh ibits regeneration of EAE transfer activity and is manifest by a lack of IL-2 mRNA accumulation despite induction of normal levels of IL-4 m RNA. Preactivated refractory T cells were substantially more susceptib le than resting T cells to the induction of anergy. Low-density T cell activation or subcloning prolonged the duration of the refractory pha se and engendered longterm desensitization of T cells marked by a bloc kade of IL-2 production and by enhanced susceptibility to anergy. Over all, these results support the concept that postactivation refractorin ess controls the pathogenicity and differentiation of T-helper cells. (C) 1996 Academic Press, Inc.