Clonal deletion and autoreactivity in extrathymic CD4-CD8-(double negative) T cell receptor-alpha/beta T cells.
Peripheral CD4-CD8- (double negative) T cells (DNT cells) that express TCR-alpha/beta (DNT-alpha/beta cells) are expanded in some autoimmunity-prone mice, but in normal mice these cells have not been extensively studied. In this study, we isolated splenic DNT-alpha/beta cells that are Thy-1+, Ly-1+, MAC-1-, J11d-, and Ia-. Only 5% of these cells were B220+. Freshly isolated DNT-alpha/beta cells did not proliferate in MLC; however, these cells responded strongly to stimulation with matrix-bound anti-TCR-alpha/beta antibodies or Con A. After activation the cells became CD4+CD8-, acquired high reactivity in both syngeneic and allogeneic MLC, but lacked cytotoxicity. After activation the cells gradually reverted to a double-negative phenotype in culture. Surprisingly, despite high autoreactivity the analysis of TCR V beta expression revealed a near normal pattern of Mls-1a- and I-E-induced clonal deletions. These findings reveal that DNT-alpha/beta cells are subject to negative selection and that autoreactivity cannot be attributed to a general failure of clonal deletion in this T cell subpopulation. DNT-alpha/beta cells may normally remain tolerant by down-regulating the CD4 molecule.
Prud'Homme
G J
GJ
Department of Pathology, McGill University, Montreal, Canada.
Bocarro
D C
DC
Luke
E C
EC
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D005796:Genes; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta