Unusual cytotoxic activities of thymus-independent, self-antigen-specific CD8(+) T cells.
We compared the cytotoxic activities of thymus-dependent and thymus-independent CD8(+) T cells. Thymus-dependent CD8(+) T cells, which are foreign antigen specific, acquired cytotoxic activity to tumor cells with a basal dose of the antigen peptides and to hybridoma cells expressing anti-TCR mAb only after differentiation into effector cytotoxic T lymphocytes (CTL). In contrast, thymus-independent CD8(+) T cells, which have been shown to be self-antigen specific, never showed cytotoxic activity to the target cells with a basal dose of the self-antigen peptide, while they could lyse hybridoma cells expressing anti-TCR mAb even without prior antigenic stimulation. Furthermore, the ex vivo cytotoxic activity of thymus-independent CD8(+) T cells was also observed against the target cells with high doses of the antigen peptides, which were not lysed by freshly isolated thymus-dependent CD8(+) T cells. Thus it is revealed that thymus-independent, self-antigen-specific CD8(+) T cells already acquire mature CTL functions in situ but have an increased threshold of TCR-mediated signaling for activation. These differences in cytotoxic activities between thymus-dependent and thymus-independent CD8(+) T cells suggest distinct roles of the two subsets of CD8(+) T cells in vivo.
Yamada
H
H
Department of Orthopedic Surgery, Graduate School of Medical Sciences and Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
Matsuzaki
G
G
Iwamoto
Y
Y
Nomoto
K
K
D000818:Animals; D001324:Autoantigens; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D005260:Female; D006182:H-Y Antigen / Q000276:immunology; D006825:Hybridomas / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013934:Thymectomy; D013950:Thymus Gland; D013997:Time Factors
D001324:Autoantigens; D006182:H-Y Antigen; D011948:Receptors, Antigen, T-Cell