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) V beta-specific manner. This TCR V beta-specific regulation is not observed in beta 2-microglobulin-deficient mice and is inhibited, in vitro, by antibody to Qa-1. We now show that similar V beta 8-specific Qa-1-restricted CD8(+) T cells are also induced by TCV with activated CD4(+) V beta 8(+) T cells. These CD8(+) T cells specifically lyse murine or human transfectants coexpressing Qa-1 and murine TCR V beta 8. Further, CD8(+) T cell hybridoma clones generated from B10.PL mice vaccinated with a myelin basic protein-specific CD4(+)V beta 8(+) T cell done specifically recognize other CD4(+) T cells and T cell tumors that express V beta 8 and the syngeneic Qa-1(a) but not the allogeneic Qa-1(b) molecule. Thus, V beta-specific Qa-1-restricted CD8(+) T cells are induced by activated CD4(+) T cells. We suggest that these CD8(+) T cells mag function to specifically regulate activated CD4(+) T cells during immune responses.