International Immunology, Vol. 12, No. 12, 1677-1683,
December 2000
© 2000 Japanese Society for Immunology
Unusual cytotoxic activities of thymus-independent, self-antigen-specific CD8+ T cells
1 Department of Orthopedic Surgery, Graduate School of Medical Sciences and
2 Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan
Correspondence to: H. Yamada, Section for Medical Inflammation Research, Department of Cell and Molecular Biology, Sölvegatan 19, 223 62 Lund, Sweden
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.
Keywords: autoimmunity, cytotoxic T cells, nude mice, transgenic mice
3 Present address: Section for Medical Inflammation Research, Department of Cell and Molecular Biology, Sölvegatan 19, 223 62 Lund, Sweden
Transmitting editor: H. R. MacDonald
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