Syngeneic Fetal Cells Research Articles

Maternal cell‐mediated cytolysis of CMV‐infected fetal cells and the outcome of pregnancy in the guinea pig

Cytolytic recognition of CMV-infected syngeneic fetal guinea pig cells by maternal peripheral blood mononuclear cells (PBMC) was suppressed late in pregnancies of uninfected guinea pig breeders with less than 25% conceptus loss. A small subset of less successful uninfected pregnancies with greater than or equal to 50% fetal wastage exhibited only partial suppression of cytolytic activity against CMV-infected fetal cells. Primary CMV infection of dams extending into early pregnancy induced augmented cytolysis of CMV-infected fetal cells, but not MA104 NK cell targets, throughout gestation and resulted in 70% loss of conceptus. Decreased suppression of cytolytic activity against CMV-infected fetal cells in uninfected pregnancy was also associated with runting of newborn pups, which was not as severe as that observed in congenitally CMV-exposed or CMV-infected pups. Congenitally infected pups were affected more than their exposed but uninfected litter mates. Lack of suppression of cytolysis of CMV-infected syngeneic fetal cells, whether spontaneous or CMV-infection-induced, appears to be associated with poor pregnancy outcome.

Inhibition of tumor growth and metastases in mice bearing a malignant fibrosarcoma by T cell-mediated immune response to oncofetal antigens.

ABSTRACT: The presence of fetal antigens on a wide variety of tumors has been well‐documented it has been attributed, for the most part, to de‐repression of genes normally operative in the early stages of embryonic development. Controversy still exists, however, about the role of fetal antigens in antitumor immunity. It is not clear whether the tumor inhibition shown in some systems is due to an immune response. In the present study, conducted in a weakly immunogenic Lewis T241 fibrosarcoma, syngeneic for C57B1/ 6J mice, immunization of normal mice with syneneic fetal cells resulted in striking inhibition of growth and metastases of tumors. On the other hand, immunization with syngeneic normal, adult spleen cells or with allogeneic A/J fetal cells did not inhibit tumor growth or metastases. Mice that had gone through single pregnancy also showed inhibition in tumor growth and metastases. Immunization of female mice with syngeneic tumor cells or fetal cells, prior to pregnancy, resulted in a high incidence of fetal death in these mice. Further studies showed that tumor inhibitory response evoked by fetal cell immunization was due to fetal antigens the male‐specific HY antigen was not responsible for antitumor response. When tumor cells were mixed with spleen cells from fetal antigen‐immunized mice and then injected into normal mice (Winn neutralization assay), significant inhibition of tumor growth and metastases was observed. In this assay, mixing tumor cells with syngeneic fetal cells, normal adult spleen cells, or spleen cells from C57 mice immunized with allogeneic fetal cells did not inhibit the tumor growth or metastases. These results show that inhibition in tumor growth and metastases, following fetal cell immunization, was due to a specific immune response to the oncofetal antigens involved. Analysis of effector cells showed them to be T cells of Lyt‐1+ and Lyt‐2− phenotype.

Host recognition of fetal antigens: do they induce specific antibodies?

The purpose of this study was to ascertain whether the protection afforded to adult mice against the induction and growth of 3-methylcholanthrene-induced tumours by prior exposure to syngeneic fetal cells has an immunological basis. Adult CBA mice were inoculated with fetal cells according to a variety of protocols and the sera were tested for their ability to bind to fetal and adult tissue cells, using a staphylococcal protein A binding assay. All 10 sera tested showed some degree of binding though this varied from strong to weak, and there was some cross-reactivity with adult thymic cells but relatively little with adult spleen cells. Absorption studies were carried out with one of these sera and with two others raised against testicular and thymic cells, respectively. The absorption patterns obtained so far suggest that fetal cells possess at least three, and possibly up to five, distinct antigens. Although none of the anti-fetal sera were produced with a sensitizing protocol identical with that used in in vivo protection, some of them were so close as to suggest that protection is associated with, and perhaps causally related to, these IgG antibodies. The in vitro evidence presented here, together with the in vivo data of P. B. Medawar & R. Hunt, shows that antigens are shared between fetal cells and adult thymic and testicular cells. It therefore lends support to the notion that the production of a vaccine against anaplastic neoplasms, using immunogens derived from adult tissues, is within the realms of possibility.

T-Cell-Mediated Antitumor Immune Response Induced by Oncofetal Antigens<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>

The possibility that fetal antigens take part in tumor immunity has been investigated to a limited extent, but the results of these studies have been controversial. It is not clear that tumor inhibition shown in some systems is due to an immune reaction. In the present study, performed in a weakly immunogenic tumor system (Lewis T241 fibrosarcoma in inbred C57BL/6J mice), immunization of mice with syngeneic fetal cells resulted in striking inhibition of growth and metastases of tumors. Mice that had gone through single pregnancies also showed a decreased rate of tumor growth and tumor metastases. Further studies have shown that the tumor inhibitory response evoked by fetal cell immunization is due to fetal antigens, and the male specific HY antigen is not responsible for antitumor response. Injection of tumor cells mixed with spleen cells from mice immunized with syngeneic fetal cells into normal mice resulted in significant inhibition of tumor growth and metastases in the Winn neutralization assay. Syngeneic fetal cells, normal adult spleen cells, or spleen cells from C57BL/6 mice immunized with allogeneic fetal cells did not inhibit tumor growth or metastases. These results show that tumor inhibition following fetal cell immunization is due to an immune reaction and is not due to a nonimmune physiologic process. Further analysis of effector cells showed them to be of the T-cell type.