Activation of cytotoxic T cells by nonstimulating tumor cells and spleen cell factor(s).

Abstract

The ability of three cultured mouse tumor lines to stimulate a cytotoxic response in 5-day cultures of allogeneic lymph node cells was studied with a 5"Cr release assay. Two lines of mesenchymal origin, P815 and EL-4, were found to be highly stimulatory, whereas the third cell line, CaDZ, a mammary wand epithelial tumor, did not stimulate over a wide range of cell concentration. CaD2 cells were shown to contain major antigens similar to those of P815 cells by the specific lysis of both cells by lymphocytes activated to H-2d-bearing peritoneal cells. UV-irradiated P815-cells, like y-irradiated CaD2 cells, did not stimulate a cytotoxic response, but both cell lines were found to stimulate a full and specific response to allogeneic lymph node cells if these mixed cultures were supplemented with a stipernatant harvested from concanavalin A-stimulated spleen cells.We have postulated that a specialized stimulator cell designated as S+ is required for T cell activation (1). Antigen presented on the surface of the S+ cell should facilitate the interaction of the stimulator cell with the potentially responsive T cell clone. Thus, T cell activation was thought to require antigen recognition in conjunction with the delivery of an inductive stimulus from the S+ cell. The production of the inductive agent by the stimulator cell or its delivery to the responsive T cell must usually require metabolic activity of the S+ cell (refs. 2

The immunogenicity of tumour cells

“…For example, similar results have been reported for another C57B1/6 tumour, Lewis lung carcinoma (23). Furthermore, the immunogenicity of tumours is not strictly related to their origin from lymphoreticular or other cell types, as originally proposed by Talmage and coworkers (24). For example, the MC-2 sarcoma (21) and UV-induced fibrosarcomas (which bear tumour-specific antigens that appear to be altered MHC Class 1 antigens (25)) are highly immunogenic in allogeneic and syngeneic mice, respectively, while many fresh human leukaemic cell populations and cell lines are poorly allostimulatory (22; 26; 27).…”

“…Talmage and coworkers (24) reported that the generation of allogeneic cytotoxic T cell responses to tumours of other than bonemarrow origin occurred in the presence, but not in the absence, of exogenous lymphokine. A similar result was obtained with B16 melanoma by Ashley et al (21) although not by Heath and Boyle (19).…”

CD80 transfected human hepatocellular carcinoma cells activate cytotoxic T lymphocytes to target HCC cells with shared tumor antigens

“…signals from co-stimulatory molecules) (15)(16)(17). This finding has provided a rationale for the introduction of genes encoding co-stimulatory molecules into tumor cells to increase their immunogenicity and vaccination potential.…”

HUMAN ALLOGENEIC RESPONSES: LYMPHOKINE REQUIREMENT FOR THE IN VITRO GENERATION OF SPECIFIC CYTOTOXIC RESPONSES TO A MALIGNANT MELANOMA CELL LINE

“…Thus, LK is required for the generation of cytotoxic responses to alloantigens (Talmage et al, 1977;Lafferty, Andrus and Prowse, 1980), tumour-associated antigens (Warren and Lafferty, 1979;Mills and Paetkau, 1980) and hapten-modified syngeneic cells (Wagner et al, 1980;Gillis and Watson, 1981). The in vitro generation of specific cytotoxic responses by human lymphocytes to xenogeneic cells is also dependent upon LK (Warren, 1981).…”