Soluble Helper Factor(s) Participates in the Generation of Cell Mediated Cytotoxicity Directed against Syngeneic Tumor Cells

Abstract

Abstract Data presented here suggest that one mechanism by which cytotoxic T lymphocytes are generated against certain syngeneic tumors may involve collaboration between pre-killer T cells and helper T cells via a soluble helper factor. Furthermore both lymphocyte-defined as well as cytotoxicity-defined antigens expressed on tumor cells may be involved in stimulating the generation of specific cytotoxic T cells. A lymphoma cell line (CH-1) derived from an SJL mouse stimulates both a syngeneic proliferative and cytotoxic response. However, heattreatment of the CH-1 cells, which is known to functionally inactivate lymphocyte-defined antigens, reduced significantly the ability of such cells to stimulate proliferation and the generation of cytotoxic T cells. The addition of supernatant fluids from either mixed lymphocyte cultures or from cultures in which syngeneic lymph node cells were sensitized against CH-1 tumor cells, restored the ability of heat-treated tumor cells to stimulate a full syngeneic cytotoxic response. The degree of T cell specific cytotoxicity that was generated was dependent in part on the concentration of helper factor(s) added to the cultures. Furthermore, supernatant fluids containing helper activity were not able to stimulate responder cell cytotoxicity in the absence of heat-treated CH-1 cells. The helper activity, detected in cultures where SJL lymph node cells were stimulated by CH-1 cells, appears to be similar to that present in supernates from allogeneic MLC since neither are antigen specific nor H-2 restricted in their ability to assist in the development of cytotoxic T cells.