Proliferative and cytotoxic responses of human peripheral blood lymphocytes to autologous malignant effusions. An analysis at the clonal level.

Abstract

Peripheral blood lymphocytes from five patients were stimulated initially in mixed lymphocyte:tumour culture (MLTC) with autologous malignant effusions and cloned by limiting dilution in interleukin-2 prior to phenotyping and assay for different functional capabilities namely proliferative responsiveness to autologous and allogeneic tumours in the primed lymphocyte test (PLT) and cytotoxicity (CTX) toward a range of fresh tumour and cell line targets. For individual clones the two functional activities tended to be mutually exclusive. Clones (or 'cloids' containing more than one PLT precursor) from three of four tumours analysed were responsive to autologous tumour cells in the PLT of which two shared antigens with allogeneic tumours of similar tissue provenance. All phenotyped PLT positive clones were T3+T4+T8-. Cytotoxic clones were generated from all MLTCs. Their target cell repertoire (based on an analysis of greater than 30) was generally broad including cell lines sensitive to natural killer (NK) cells, and less frequently and to a weaker extent, fresh autologous and allogeneic tumours. An ovarian carcinoma was exceptional, insofar as the CTX of 8/9 clones was apparently restricted to the autologous tumour. Phenotypically cytotoxic clones were T3+T4-T8+, less usually T3+T4+T8-, but invariably B73.1- (a monoclonal antibody reactive with the peripheral blood NK subset). Analysis at the clonal level emphasises the diversity of responses to putative human tumour-associated antigens, and the need to identify the critical functionally active molecules in the MLTC.