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) cell s is described. Killing was performed both by direct cytolytic mechanisms a nd by apoptosis. The peculiar characteristic of these effecters was their c apability of lysing only interferon (IFN)-gamma-treated NSCLC target cells, expressing high numbers of HLA class I molecules. Analysis at the clonal l evel confirmed that cytolytic capability was distributed clonotypically. Th e addition of anti-HLA class I monoclonal IgM abrogated the susceptibility to lysis. Notably, the CD4-mediated cytolytic effect on IFN-gamma-treated t argets 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. Th ese findings suggested a direct role of HLA class I expression in the recog nition of autologous cancer cells mediated by cytolytic CD4(+) cells. (C) 1 999 Academic Press.