In vivo anergized CD4(+) T cells express perturbed AP-1 and NF-kappa B transcription factors

Anergy is a major mechanism to ensure antigen-specific tolerance in T lymphocytes in the adult, In vivo, anergy has mainly been studied at the cellular level, In this study, we used the T-cell-activating superantigen staphylococcal enterotoxin A (SEA) to investigate molecular mechanisms of T-lymphocyte anergy in vivo, Injection of SEA to adult mice activates CD4(+) T cells expressing certain T-cell receptor (TCR) variable region beta-chain families and induces strong and rapid production of interleukin 2 (IL-2), In contrast, repeated injections of SEA cause CD4(+) T-cell deletion and anergy in the remaining CD4(+) T cells, characterized by reduced expression of IL-2 at mRNA and protein levels, We analyzed expression of AP-1, NF-kappa B, NF-AT, and octamer binding transcription factors, which are known to be involved in the regulation of IL-2 gene promoter activity, Large amounts of AP-1 and NF-kappa B and significant quantities of NF-AT were induced in SEA-activated CD4(+) spleen T cells, whereas Oct-1 and Oct-2 DNA binding activity was similar in both resting and activated T cells, In contrast, anergic CD4(+) T cells contained severely reduced levels of AP-1 and Fos/Jun-containing NF-AT complexes but expressed significant amounts of NF-kappa B and Oct binding proteins after SEA stimulation, Resolution of the NF-kappa B complex demonstrated predominant expression of p50-p65 heterodimers in activated CD4(+) T cells, while anergic cells mainly expressed the transcriptionally inactive p50 homodimer, These alterations of transcription factors are likely to be responsible for repression of IL-2 in anergic T cells.