Cytotoxicity of Fresh NKI . 1 + T Cell Receptor c / A 8 + Thymocytes against a CD 4 + 8 + Thymocyte Population Associated with Intact Fas Antigen Expression on the Target

Recent studies have revealed that 10-20% of CD4+8 or CD4-8thymocyte populations contain NKI.1 + T cell receptor (TCR)-cff~ + cells. This subpopulation shows characteristics that are different from NKI.1CD4 § or NKI.1CD8 + T calls and seems to have developed in a manner different from NKI.1T cells. Although extensive studies have been performed on the NKI.1 + TCR-od~8 + thymocytes, the physiological role of the NKI.1 + TCR-c~/~/+ thymocytes has been totally unclear. In the present study, we found that fleshly isolated NKI.1 + TCR-odB + thymocytes, but neither whole thymocytes nor lymph node T cells, directly killed CD4 +8 § thymocytes from normal syngeneic or allogeneic mice by using a long-term cytotoxic assay in which flow cytometry was used to detect the cytotoxidty. However, only weak cytotoxicity was detected against thymocytes from lpr mice on which the Fas antigen that transduces signals for apoptosis into the cells is not expressed. Furthermore, the NKI.1 + TCR-ot/B + thymocytes exhibited high cytotoxicity against T lymphoma targets transfected withj~s genes as compared with the parental T lymphoma targets or target cells transfected with mutatedJas genes, which lack the function of transducing signals. On the other hand, NKI.1 § effector thymocytes from gld mice that carry a point mutation in Fas ligand did not kill thymocyte targets from normal mice. The present findings, thus, consistently suggest that the NKI.1 + TCR-ot/~8 + thymocytes kill a subpopulation among CD4+8 + thymocytes via Fas antigen and in this way regulate generation of T lineage cells in the thymus.