The "natural resistance" to bone marrow allografts in normal and athymic nude rats. Rapid cytotoxic reactions both in vivo and in vitro.

Abstract

To elucidate the rapid destruction of allogeneic bone marrow (BM) grafts in nonsensitized rats we have assessed: (a) the 21-h tissue localization of 51Cr-labeled allogeneic vs. syngeneic BM cells, (b) the ability of allogeneic BM cells to proliferate in the BM or irradiated recipients, (c) the survival of allogeneic vs. syngeneic BM cells in cell-impermeable diffusion chambers implanted into the peritoneal cavity of rats, and (d) the destruction of allogeneic vs. syngeneic labeled BM cells in vitro by effector cells from various lympho-myeloid tissues. Some allogeneic BM cells were destroyed within 24 h after transfer to athymic nude rats, thus demonstrating the thymus independence of the cytotoxicity. Furthermore, allogeneic BM cells also failed to proliferate in the BM of irradiated recipients. However, the survival of allogeneic BM cells was not impaired if they were sheltered from host cells within cell-impermeable diffusion chambers over a culture period of 4 days. But when the allogeneic BM cells were similarly cultured in hosts presensitized against the BM donor, a substantial reduction in BM cell survival was observed. The effector cells of allogeneic BM cytotoxicity (ABC) were present in the spleen because PVG-rnu spleen cells were highly effective in lyzing BM cells from the AO, but not the PVG strain in vitro after only 4 h of culture. Some ABC activity in vitro was also found for peripheral blood lymphocytes and lymph node cells, but not for BM cells themselves. Taken as a whole these data provide firm evidence that the "natural resistance" to BM allografts is basically different from conventional immune responses, and in most, but not all respects resembles natural killer activity.