In vitro sensitization to embryonic antigens

Abstract

Lymphoid cells from virgin, untreated BALB/c mice cultured 5 days on 12- or 13-day syngeneic mouse embryo fibroblasts (MEF) or on cells from a syngeneic 3-methylcholanthrene-induced mouse sarcoma (1315) were cytotoxic for 1315 tumor target cells when tested with a microcytotoxicity assay. They did not kill embryo or skin fibroblast target cells. Lymphoid cells cultured with 11-, 14- or 17-day MEF were not cytotoxic for cells from the 1315 tumor, from embryo or from adult skin. Lymphoid cells from multiparous BALB/c mice cultured on 11-, 12- or 13-day MEF, on line 1315 sarcoma cells or on skin fibroblasts were cytotoxic for tumor target cells. MEF were killed by multipara lymphoid cells that had been cultured on 11-, 12- or 13-day MEF or on the 1315 tumor line. Multipara lymphoid cells cultured on 1315 cells or 12-day MEF were cytotoxic for adult skin fibroblasts, while multipara lymphoid cells cultured on 14- or 15-day MEF were not cytotoxic for any of the target cells. The data thus indicate that lymphoid cells can mediate both primary and secondary immune reaction in vitro to antigens shared by neoplastic and normal embryonic cells, and that the primary reactions appear to be more specific to putatively embryonic tumor antigen(s) than the secondary ones.

Effects of presensitization in vivo on cell‐mediated responses to embryonic antigens in vitro

“…* pc0.05 by Student's t-test; ** p <0.01. sensitized effector cells. Our results thus confirm earlier studies on generation of lymphoid cells cytotoxic to murine fibrosarcomas (Friend et al, 1976) and a variety of murine tumors (Chisom et al, 1976) by in vitro co-cultivation with syngeneic embryo cells.…”

“…Earlier attempts to increase the cytotoxicity of spleen cells from intrastrain pregnant mice by cocultivation in vitro on embryo cells gave results similar to ours (Friend et al, 1976). Effector:target cell ratios greater than 200:l were necessary to demonstrate cytotoxicity to embryo target cells after culture and no specific increase of activity was demonstrated as spleen cells co-cultivated with adult fibroblasts were also cytotoxic.…”

“…We used both a microcytotoxicity assay with a 40-h incubation period (Hellstrom and Hellstrom, 1976) and a 61Cr-release assay with a 18-24 h incubation period (Steele et al, 1975~) to measure cellmediated immunity to attached target cells. The same target cells and spleen cell :target cell ratios were used in both assays.…”

“…In order to examine the cellmediated response to antigens shared by colon carcinomas and embryo cells, we adapted available techniques for the in vitro induction of cytotoxic lymphocytes by co-cultivation with embryo cells (Friend et al, 1976;Chisom et al, 1976;Gorczynski, 1976a). We wished to increase the efficiency of the sensitization either through expansion of antigen-committed cells by in vivo exposure to the embryonic antigens or, if induction of suppressor cells also occurred, by finding means to circumvent this induction.…”

Tumor Suppression by DNA Base Excision Repair

“…A small, but probably steady production of carcinogenic radicals is a price to be paid to aerobic metabolism. 3-methylcholantrene-induced mouse sarcomas) can share common antigens against which lymphoid cells mediate both primary and secondary immune reactions [96] and immunization with transformed MEFs may protect in some cases mice from subsequent challenge with live tumor cells [97]. For example, mutations in the tumor suppressor genes p53 and INK4a are common, albeit not sufficient, events in the spontaneous immortalization/transformation of normal fibroblasts [56][57][58]86,87] and those are precisely the two most frequently inactivated tumor suppressor genes in human cancer, irrespective of tumor type, site, and patient age [88,89].…”