T-T ANTIGEN PRESENTATION BY ACTIVATED MURINE CD8(-CELLS INDUCES ANERGY AND APOPTOSIS() T)

Using an IL-2-secreting, noncytolytic, H-Y-specific, CD8(+) T cell clo ne, the functional consequences of Ag presentation by T cells to T cel ls mere investigated, Incubation of the T cells with H-Y-soluble pepti de led to nonresponsiveness to Ag rechallenge, This was due to the sim ultaneous induction of apoptosis, involving approximately 40% of the T cells, and of anergy in the surviving cells, These effects were stric tly dependent upon bidirectional T:T presentation, in that exposure of C6 cells to peptide-pulsed T cells from the same clone induced prolif eration but not apoptosis or anergy. The inhibitory effects of T:T pre sentation were not due to a lack of costimulation, since the T cells e xpressed levels of CD80 and CD86 higher than those detected on culture d dendritic cells and equipped them to function as efficient APCs for primary CD8(+) T cell responses, Following incubation with soluble pep tide, CD80 expression increased, and high levels of CTLA-4 (CD152) exp ression were induced, Although addition of anti-CTLA-4 Ab augmented pr oliferation in response to soluble peptide, no protection from apoptos is or anergy was observed, Neither Fas nor TNF-alpha was expressed/pro duced by the C6 cells, and coligation of MHC class I molecules and TCR failed to reproduce the effects of T:T presentation, Taken together, these data suggest that T:T Ag presentation induces anergy and apoptos is in murine CD8(+) T cells and may reflect the regulatory consequence s of T:T interactions in the course of clonal expansion in vivo.