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 specific for myelin basic protein exhibit a postactivation refractory phase during which antigenic restimulation elicits proliferation without production of IL-2. Herein, we show that postactivation refractoriness inhibits regeneration of EAE transfer activity and is manifest by a lack of IL-2 mRNA accumulation despite induction of normal levels of IL-4 mRNA. Preactivated refractory T cells were substantially more susceptible than resting T cells to the induction of anergy. Low-density T cell activation or subcloning prolonged the duration of the refractory phase and engendered long-term desensitization of T cells marked by a blockade of IL-2 production and by enhanced susceptibility to anergy. Overall, these results support the concept that postactivation refractoriness controls the pathogenicity and differentiation of T-helper cells.
Mannie
M D
MD
Department of Microbiology and Immunology, East Carolina University School of Medicine, North Carolina, USA.
White
G A
GA
Lake
K R
KR
Nardella
J P
JP
Marinakis
C A
CA
McConnell
T J
TJ
D000818:Animals; D002460:Cell Line; D017635:Clonal Anergy; D006168:Guinea Pigs; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D004676:Myelin Basic Protein / Q000276:immunology*; D012333:RNA, Messenger; D051381:Rats; D011917:Rats, Inbred Lew; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013997:Time Factors
D007376:Interleukin-2; D004676:Myelin Basic Protein; D012333:RNA, Messenger; D015847:Interleukin-4