STAPHYLOCOCCUS-AUREUS ENTEROTOXIN MEDIATED SPECIFIC NONRESPONSIVENESS OF HUMAN T-CELLS

Exotoxins produced by certain strains of Staphylococcus aureus are able to both stimulate and induce non-responsiveness in T cells expressing specific T cell antigen receptor V-beta gene elements. The exposure of human CD4+ T cells to the appropriate enterotoxin rendered them anergic to restimulation with their natural ligand, although responsiveness to exogenous IL-2 remained intact. The loss of antigen-dependent proliferation was associated with the down-regulation of the TCR complex that was paralleled by enhanced cell surface CD2 and CD25. Further analysis of the phenotypic changes revealed that membrane levels of CD28 were increased only on activation, suggesting a differential expression of this protein on activated and anergic T cells. During the induction of anergy it was observed that the synthesis of the lymphokines IL-2, IL-4 and IFN-gamma was differentially regulated. IL-4 and IFN-gamma, but not IL-2 were detected in the supernatants of overnight cultures of T cells exposed to tolerising concentrations of toxin. Transcription of IL-4, as determined by polymerase chain reaction at selected intervals, was elevated during the induction of anergy and accounted for the presence of the protein in the supernatants. In contrast, no tight coupling was observed between protein and mRNA levels for IL-2, suggesting post-translational regulation.