T cell vaccination induces T cell receptor Vbeta-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) Vbeta-specific manner. This TCR Vbeta-specific regulation is not observed in beta2-microglobulin-deficient mice and is inhibited, in vitro, by antibody to Qa-1. We now show that similar Vbeta8-specific Qa-1-restricted CD8(+) T cells are also induced by TCV with activated CD4(+) Vbeta8(+) T cells. These CD8(+) T cells specifically lyse murine or human transfectants coexpressing Qa-1 and murine TCR Vbeta8. Further, CD8(+) T cell hybridoma clones generated from B10.PL mice vaccinated with a myelin basic protein-specific CD4(+)Vbeta8(+) T cell clone specifically recognize other CD4(+) T cells and T cell tumors that express Vbeta8 and the syngeneic Qa-1(a) but not the allogeneic Qa-1(b) molecule. Thus, Vbeta-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.
Jiang
H
H
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Kashleva
H
H
Xu
L X
LX
Forman
J
J
Flaherty
L
L
Pernis
B
B
Braunstein
N S
NS
Chess
L
L
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D051379:Mice; D008806:Mice, Inbred AKR; D008815:Mice, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000276:immunology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D001324:Autoantigens; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; C032907:Q surface antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; D018089:Superantigens