Cytotoxic T lymphocyte hybridomas that mediate specific tumor-cell lysis in vitro.

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Abstract
Cytotoxic hybridomas were generated by polyethylene glycol-induced fusion of cytotoxic T lymphocytes (CTL) and BW5147 [mouse thymic] lymphoma cells. The CTL populations used for fusion were obtained from BALB/c (H-2d) mice primed with leukemia EL4 of C57BL/6 (H-2b) and restimulated in vivo or in vitro. To circumvent possible CTL-mediated nonspecific lysis of BW5147 cells during fusion, the CTL were transiently inactivated by trypsin prior to fusion. Four cytolytically active hybridomas were obtained, cloned and subcloned. Hybrid clones lysed all H-2b leukemic target cells tested, but not lipopolysaccharide- or concanavalin A-stimulated C57BL/6 lymphoblasts or non-H-2b target tumor cells. The mechanism of hybridoma-mediated killing of target cells in vitro appears to be similar to that of parental CTL, although some differences were observed. The hybridomas appear to possess neither natural killing nor antibody-dependent cytolytic activity. Clones of hybrids propagated in culture for over 6 mo. without the addition of known external stimulus (i.e., independent of cell growth factor and antigen) exhibit specific lytic activity against H-2b tumor cells. Such autonomous hybridomas will provide a tool for studying the mechanism of CTL-mediated lysis and the nature of the CTL receptors.