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.