Abstract
Objectives: CD8+ T cells generated by mixed lymphocyte culture exhibit cytotoxic activity toward some allogeneic tumor (eg, mastocytoma, leukemia, and lymphoma) cells and certain types (eg, mastocytoma, lymphoma, and fibroblastic) of virally infected cells in vitro. In contrast, noncytotoxic CD4+, but not cytotoxic CD8+, T cells are essential for allograft (eg, heart, islets, and skin or some fibrosarcoma cells) rejection; and clearance of influenza or Sendai virus from virus-infected respiratory epithelium is normal or slightly delayed after a primary viral challenge of CD8 knockout mice, implying the cell type-dependent cytotoxicity of CTL.
Methods: To address this possibility, we here determined cytotoxic repertoire of CD8+ CTLs using various kinds of allogeneic cells (eg, lymphoblasts, lymphoid tumor cells, fibroblasts, squamous cell carcinoma, and fibrosarcoma cells) and syngeneic cells persistently infected with variant Sendai virus as targets.
Results: The target cells expressed the allo-MHC or viral Ag; the cytotoxic activity of CTL against 51Cr-labeled CTL-susceptible targets was suppressed by the addition of unlabeled another targets; but Ag-specific CTLs exhibited a differential cytotoxic repertoire: CTLs were highly cytotoxic against mastocytoma, lymphoid, or fibroblastic cells, whereas the CTLs were inactive toward squamous cell carcinoma or fibrosarcoma cells.
Conclusion: These results suggest that resistance of epithelial or some mesenchyme cells to the CTL-mediated cytotoxicity may account for CD4+ (noncytotoxic) T cell-dependent allograft rejection or almost normal clearance of influenza or Sendai viruses from infected epithelium of CD8+ (cytotoxic) T cell-depleted mice.