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T:T Antigen Presentation by Activated Murine CD8⁺ T Cells Induces Anergy and Apoptosis¹

Jian-Guo Chai^*, Istvan Bartok, Diane Scott, Julian Dyson and Robert Lechler^2,*

^* Department of Immunology, Division of Medicine, Hammersmith Hospital, Imperial College of Science, Technology, and Medicine; and Transplantation Biology Group, Medical Research Council Clinical Sciences Centre, London, United Kingdom

Using an IL-2-secreting, noncytolytic, H-Y-specific, CD8⁺ T cell clone, the functional consequences of Ag presentation by T cells to T cells were investigated. Incubation of the T cells with H-Y-soluble peptide led to nonresponsiveness to Ag rechallenge. This was due to the simultaneous induction of apoptosis, involving approximately 40% of the T cells, and of anergy in the surviving cells. These effects were strictly dependent upon bidirectional T:T presentation, in that exposure of C6 cells to peptide-pulsed T cells from the same clone induced proliferation but not apoptosis or anergy. The inhibitory effects of T:T presentation were not due to a lack of costimulation, since the T cells expressed levels of CD80 and CD86 higher than those detected on cultured dendritic cells and equipped them to function as efficient APCs for primary CD8⁺ T cell responses. Following incubation with soluble peptide, CD80 expression increased, and high levels of CTLA-4 (CD152) expression were induced. Although addition of anti-CTLA-4 Ab augmented proliferation in response to soluble peptide, no protection from apoptosis or anergy was observed. Neither Fas nor TNF- was expressed/produced 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 apoptosis in murine CD8⁺ T cells and may reflect the regulatory consequences of T:T interactions in the course of clonal expansion in vivo.

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