IL-2 secretion and T cell clonal anergy are induced by distinct biochemical pathways

Steven D. Norton, David E. Hovinen, Marc Jenkins

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

In Th1 clones, TCR occupancy together with a costimulatory signal from APC results in IL-2 production. TCR occupancy alone results in unresponsiveness (anergy) to antigenic stimulation, a phenomenon that may be important for self-tolerance in vivo. Inasmuch as inositol phosphate production occurs during the induction of anergy other biochemical signals must be necessary for IL-2 production. Here we assess the role of tyrosine-specific protein kinases using the specific inhibitor, genistein. IL-2 secretion and responsiveness were very dependent on tyrosine-specific protein kinase activation and could be completely blocked under conditions where inositol phosphate generation occurred normally. Although anergy induction could also be blocked by inhibition of tyrosine-specific protein kinase activation this probably occurred indirectly via inhibition of inositol phospholipid hydrolysis. The differential susceptibility of IL-2 secretion and anergy induction to inhibition by genistein indicates that positive and negative outcomes of TCR occupancy may be mediated by distinct biochemical pathways.

Original languageEnglish (US)
Pages (from-to)1125-1129
Number of pages5
JournalJournal of Immunology
Volume146
Issue number4
StatePublished - 1991

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