T Cell Vaccination Induces T Cell Receptor Vβ -specific Qa-1-Restricted Regulatory CD8+T Cells

Vaccination of mice with activated autoantigen-reactive CD4+T cells (T cell vaccination, TCV) has been shown to induce protection from the subsequent induction of a variety of experimental autoimmune diseases, including experimental allergic encephalomyelitis (EAE). Although the mechanisms involved in TCV-mediated protection are not completely known, there is some evidence that TCV induces CD8+regulatory T cells that are specific for pathogenic CD4+T cells. Previously, we demonstrated that, after superantigen administration in vivo, CD8+T cells emerge that preferentially lyse and regulate activated autologous CD4+T cells in a T cell receptor (TCR) Vβ -specific manner. This TCR Vβ -specific regulation is not observed in β2-microglobulin-deficient mice and is inhibited, in vitro, by antibody to Qa-1. We now show that similar Vβ 8-specific Qa-1-restricted CD8+T cells are also induced by TCV with activated CD4+Vβ 8+T cells. These CD8+T cells specifically lyse murine or human transfectants coexpressing Qa-1 and murine TCR Vβ 8. Further, CD8+T cell hybridoma clones generated from B10.PL mice vaccinated with a myelin basic protein-specific CD4+Vβ 8+T cell clone specifically recognize other CD4+T cells and T cell tumors that express Vβ 8 and the syngeneic Qa-1abut not the allogeneic Qa-1bmolecule. Thus, Vβ -specific Qa-1-restricted CD8+T cells are induced by activated CD4+T cells. We suggest that these CD8+T cells may function to specifically regulate activated CD4+T cells during immune responses.