Rapid in Vivo Destruction of Semi-Syngeneic and Allogeneic Cells by Nonimmunized Mice as a Consequence of Nonidentity at H-2

Abstract

By monitoring the death and metastatic distribution of ¹³¹I-iododeoxyuridine (IUdR) prelabeled H-2^d leukemia cells, hybrid and allogeneic resistance were studied in vivo. All mice tested were able to recognize and kill leukemia cells which were not H-2 identical with self. Resistance was found, not only against completely allogeneic leukemia cells, but also against semi-syngeneic parental strain cells in F₁ hybrid mice. This resistance against semi-syngeneic and allogeneic cells was manifest in two ways. First, the total survival of incompatible cells as determined by whole-body γ counting was less than the survival in H-2 identical hosts, with the killing of the grafted cells apparent within 24 hr of injection. Second, colonization of the spleen by the H-2 homozygous leukemia cells was inhibited in H-2 heterozygous and H-2 incompatible mice when measured as early as 3 days after injection. This splenic rejection of grafted leukemia cells was organ specific because the sharp reduction of radioactivity seen in the spleen was not paralleled by a concomitant loss in other organs such as the liver. Differences at either the K through I-B regions of the H-2 gene complex or the D region alone were sufficient to initiate rejection. Although all nonirradiated mice showed early recognition and rejection of cells which were not H-2 identical with self, irradiation abolished rejection in some strains of mice whereas in others the rejection process was unaffected. While differences at H-2 provided the targets for recognition, non-H-2 genes determined the susceptibility of the rejection process to irradiation.