Anergic T cells act as suppressor cells in vitro and in vivo

The potential suppressive effects of allospecific anergic T cells were inve stigated both in vitro and in vivo. Allospecific T cells were rendered unre sponsive in vitro using immobilized anti-CD3 mAb. These anergic T cells pro foundly inhibited proliferation of responsive T cells in an antigen-specifi c manner. The observed inhibition did not appear to be due to the release o f inhibitory cytokines in that secretion of IL-2, IFN-gamma, IL-4, IL-10 an d TGF-beta was greatly reduced following the induction of anergy, and neutr alizig mAb specific for IL-4, IL-10 and TGF-beta failed to reverse the inhi bition. Furthermore, the suppression mediated by anergic T cells required c ell to cell contact. In vivo, adoptive transfer of anergic T cells into rec ipients of allogeneic skin grafts led to prolonged skin graft survival. Con sistent with the lack of inhibitory cytokine production by the anergic cell s, prolongation of skin allograft rejection was not influenced by the simul taneous administration of a neutralizing anti-IL-4 antibody. These results indicate that anergic T cells can function as antigen-specific suppressor c ells both in vitro and in vivo.