T cell vaccination induces T cell receptor Vβ-specific Qa-1-restricted regulatory CD8⁺T cells

Abstract

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

Prevention of spontaneous immune-mediated diabetes development in the LEW.1AR1-iddm rat by selective CD8+ T cell transfer is associated with a cytokine shift in the pancreas-draining lymph nodes

“…There is cumulative evidence that CD8 + T cells may participate as effectors and as regulators in autoimmune diseases [16,[24][25][26][27][28]. A clear inhibitory interaction between regulatory CD8 + and autoreactive CD4 + T cells was found in experimental autoimmune encephalomyelitis [25,29] and also in human autoimmune diabetes [30][31][32]. In a mouse model of experimental autoimmune encephalomyelitis, CD8 + /CD28 − T cells provided protection by inhibiting upregulation of co-stimulatory molecules on antigenpresenting cells, thereby inhibiting activation and clonal expansion of autoaggressive CD4 + cells [26].…”

A Peptide from Heat Shock Protein 60 Is the Dominant Peptide Bound To Qa-1 in the Absence of the MHC Class Ia Leader Sequence Peptide Qdm

“…A peptide from the leader sequence of preproinsulin has been shown to bind to Qa-1 b and is recognized by Qa-1 b -restricted CTL (29). Qa-1-restricted CD8 ϩ T cells that specifically kill activated V␤8 ϩ T cells have been reported by Jiang et al (30,31). These Qa-1-restricted T cells, which were induced by vaccination with V␤8 ϩ T cells or staphylococcal enterotoxin B injection, presumably recognize Qa-1-presenting TCR-derived peptides.…”

Apportioning Blame: Autoreactive CD4+ and CD8+ T Cells in Type 1 Diabetes

“…The regulatory role played by CD8 + T cells was first proposed by data from mice where this cell subset (restricted by the Qa-1 molecule-the homologue of the human HLA-E molecule) limited or regulated many types of immune responses in vivo, including autoimmune diseases, such as experimental allergic encephalomyelitis (Jiang et al 1998). In T1D, the presence of these HLA-E-restricted CD8 + Treg cells has also been demonstrated.…”