Suppression mediated by anergic CD4(+) T cells requires stimulation by MHC-peptide complexes and can be induced in the presence of costimulation

Background. In this study, we have investigated the mechanisms involved in both the induction of suppressive anergy, the stability of the anergy induc ed, and the possible mechanisms by which the response of immunocompetent CD 4(+) T cells are suppressed. Methods. We used immobilized anti-CD3 monoclonal antibody (mAb) to induce a nergy in T helper (Th) 1 and Th0 cells reactive with MHC class II molecule H2 I-Ab. Results. We observed that suppressive anergy was induced independently of c ostimulation in Th0 but not Th1 cells. Although the anergic and suppressive states of Th0 cells were stable in the presence of exogenous interleukin-2 , this was not the case for Th1 cells. No evidence for linked epitope suppr ession was observed for any of the I-A(b) reactive cells investigated. Neit her anergy nor suppression was observed in Th0 cells upon restimulation wit h anti-CD3 in the presence of syngeneic antigen-presenting cells (APCs). Ho wever, anergy but not suppression was observed in co-cultures restimulated with anti-T-cell antigen receptor (TCR) mAbs/syngeneic APCs and suppression could be restored by the addition of I-A(b+) A-PCs. Conclusions. Overall, these data suggested that the MHC-peptide complex rec ognized by the Th0 cells was required for suppression of the response of im munocompetent cells. We propose that suppression is mediated either by down -modulation of the MHC-peptide complex recognized by the anergic T cells or that a molecule specific to the MHC-peptide/TCR interaction facilitates ne gative regulation by APC:T or T:T interactions.