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
Md. Mannie et al., 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, Cellular immunology, 172(1), 1996, pp. 108-117
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.