ANERGY INDUCTION IN HUMAN CD4-CELL CLONES BY STIMULATION WITH SOLUBLEPEPTIDES DOES NOT REQUIRE CELL-PROLIFERATION AND IS ACCOMPANIED BY ELEVATED IL4 PRODUCTION( T)

The stimulation of activated T cells with soluble peptides or peptide- pulsed T-APC in the absence of professional APC can anergize peptide-s pecific T cells. Here, we studied human T cell clones (TCCs) that eith er proliferate (T-responder) or do not proliferate (T-nonresponder) to activated T cells as antigen-presenting cells (APC) and investigated the efficacy of anergy induction in these two types of TCCs. The TCCs were specific to the p30 peptide from tetanus toroid and secreted eith er a Th0- or a Th1-like cytokine pattern. To induce anergy, the TCCs w ere first stimulated by addition of the peptides directly to the cell cultures without additional APC (T-APC). Anergy was detected by restim ulating these TCCs on professional B-APC. The proliferation, productio n of cytokines (IL2, IFN-gamma, IL4, IL5, IL10), and the cytotoxicity were measured after the first and second stimulation and compared with nonanergized control cells. Priming of TCCs by T-APC (anergy inductio n) resulted in an elevated production of IL4. This cytokine shift was also seen in the T-nonresponder TCC despite no induced proliferation. Th1-like TCCs retained their cytotoxicity after anergy induction. In c ontrast to cells first activated by B-APC, the restimulation of TCCs p rimed by T-APC lead to a drastic reduction of proliferation and cytoki ne production for both T-responder and T-nonresponder TCCs. The functi onal down-regulation of TCCs mediated by soluble peptides could be ove rcome by addition of IL2, but not by IL1 or IL4. We concluded that the induction of T-cell anergy does not require cell proliferation. (C) 1 996 Academic Press, Inc.