Rejection of Allo- or Xenografts of Lymphoid Cells by Nude Mice: T Cell Suicide as a Result of Cooperation between Histoincompatible T and B Cells

Abstract

Athymic nude mice with a BALB/c or C57BL/6 genetic background were given an i.v. injection of allo- (e.g., CBA-T6T6) or xenogeneic (rat) lymphoid cells or purified T lymphocytes. About 1 week after a phase of graft-vs-host reaction, which was manifested by an increase in size of the lymphoid organs and a proliferation of donor T cells (detected by combined immunofluorescence and autoradiography and by caryotypic analysis), the grafted cells were rejected as indicated by 1) reversion of the lymphoid organs to their original size and to the very low initial T cell content or 2) by absence of donor cell mitoses. This was closely correlated with the appearance in the nude mice sera of high titers of cytotoxic antibodies of the IgG class, specifically directed against cells of the donor strain; these sera also seemed to contain anti-donor Ia antibodies. When the allogeneic or xenogeneic lymphoid cell graft was performed on nude mice bearing two foreign skin allografts, one syngeneic and the other allogeneic to the lymphoid graft, no gross signs of skin graft rejection were observed, except after injection of rabbit serum as a source of C. This was followed by an hyperacute rejection of the skin graft syngeneic to the lymphoid graft whereas the unrelated skin graft was unaffected.Living T cells play an essential role in the strong antidonor humoral response of the nude mice, since nude mice injected with histoincompatible B cells or with lymphoid cells inactivated with slight formaldehyde fixation showed only an inconstant, very weak, and transient humoral response. The reaction of nude mice to foreign lymphoid grafts therefore implies a peculiar form of T-B cell cooperation across the histocompatibility or species barrier, in which the grafted T cells, recognizing the nude mice antigens, help the nude B cells make antibodies against the graft, thus leading to their own rejection.