Cytotoxic Properties of CD4+ T-Cell Clones Which Lyse HLA Class II Negative Autologous Non-Small-Cell Lung Cancer Cells

In this report, a subset of CD4+ cells which kills autologous HLA class I positive and HLA class II negative non-small-cell lung cancer (NSCLC) cells is described. Killing was performed both by direct cytolytic mechanisms and by apoptosis. The peculiar characteristic of these effectors was their capability of lysing only interferon (IFN)-γ-treated NSCLC target cells, expressing high numbers of HLA class I molecules. Analysis at the clonal level confirmed that cytolytic capability was distributed clonotypically. The addition of anti-HLA class I monoclonal IgM abrogated the susceptibility to lysis. Notably, the CD4-mediated cytolytic effect on IFN-γ-treated targets was incomplete. Thus cytofluorimetric DNA and HLA class I expression analyses of target cells were performed: “resistant” targets consisted of large, aneuploid cells expressing a low number of HLA class I molecules. These findings suggested a direct role of HLA class I expression in the recognition of autologous cancer cells mediated by cytolytic CD4+ cells.