Transactivation byAP- 1 Isa Molecular Target of TCell Clonal Anergy

Anergy isamechanism ofTlymphocyte tolerance induced byantigen receptor stimulation intheabsence ofco-stimulation. Anergic Tcells wereshowntohaveadefect inantigeninduced transcription oftheinterleukin-2 gene.Analysis ofthepromoter indicated that the transcription factor AP-1andits corresponding ciselement werespecifically down-regulated. Exposure ofanergic Tcells tointerleukin-2 restored bothantigen responsiveness andactivity oftheAP-1element. Inpursuing theobservations ofBillingham andcolleagues (1) onacquired immunological tolerance, Dresser showed that immunization with deaggregated foreign proteins rendered adult miceunresponsive tosubsequent antigenic challenge (2). Incontrast, thesameantigen preparation initially administered withadjuvant wasimmunogenic.Models that usetwosignals forlymphocyteactivation canpotentially explain these early observations (3, 4).Experimental evidence shows that stimulation oftheT cell receptor (TCR)together withasecond, nonantigen-specific signal, termed co