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 x 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 cytotoxicity in vitro. The other cytotoxic effector cell generated following the immunization of (AKR/J x 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 cytotoxicity in 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 activated in vitro by IL-2, TPA, and ionomycin, they cannot be propagated in vitro. The CD3-/Thy-1+ cells undergo apoptosis following prolonged culture in 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.
Sabapathy
T K
TK
Laboratory of Molecular Immunology, National University of Singapore.
Cheng
Q
Q
Hui
K M
KM
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D017252:CD3 Complex / Q000032:analysis*; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000235:genetics; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018800:Thy-1 Antigens / Q000032:analysis*; D014162:Transfection; D014407:Tumor Cells, Cultured
D017252:CD3 Complex; D006183:H-2 Antigens; D018800:Thy-1 Antigens