Characterization of Tumor-Specific Cytotoxic Effector Cells with a Novel CD3−/Thy-1+Phenotype

The introduction and expression of allogeneic MHC class I genes in tumors can generate tumor-specific immunity which subsequently results in the regression of parental tumors. Immunization of naive (AKR/J × C57BL/6)F1 mice with H-2Kb-transformed K36 tumor cells was found to render recipient mice immune to a subsequent challenge by parental K36 tumor cells. Two types of cytotoxic T effector cells were demonstrated in these immune mice. One of the cytotoxic effector cells generated against the K36 tumor cells is the conventional CD3+cells, and these account for approximately one-third of the total observed tumor-specific cytotoxicityin vitro.The other cytotoxic effector cell generated following the immunization of (AKR/J × C57BL/6)F1 mice with the H-2Kb-transformed K36 cells had the CD3−/Thy-1+phenotype, and accounted for the remaining two-thirds of the observed tumor-specific cytotoxicityin vitro.These CD3−/Thy-1+cells can lyse parental K36 tumor cells in a tumor-specific fashion, and tumor-specific immunity can be adoptively transferred to naive animals via the CD3−/Thy-1+cells. In contrast to CD3+CTL, CD3−/Thy-1+cells express CD45RBlow, Ly-6Chigh, and HSA molecules. Although the CD3−/Thy-1+cells can be activatedin vitroby IL-2, TPA, and ionomycin, they cannot be propagatedin vitro.The CD3−/Thy-1+cells undergo apoptosis following prolonged culturein vitro.At present, the exact mechanism(s) by which CD3−/Thy-1+cells can mediate tumor-specific cell lysis in the absence of identifiable T cell receptor molecules is unknown; nevertheless, these data suggest the existence of a novel T cell type to combat tumors.