Studies on the Immunologic Unresponsiveness during the Secondary Disease Period of Lethally Irradiated Mice Protected by Homologous Bone Marrow

Abstract

Summary The survival of lethally x-irradiated mice protected by isologous or homologous bone marrow therapy was studied. To eliminate the mortality due to primary disease the arbitrary period beginning 21 days after irradiation was chosen and survival was followed for an additional 90 days. It was observed that those groups of mice “saved” by homologous bone marrow consistently fared less well than those protected by isologous marrow. The i.v. administration of 10 × 106 isologous lymphocytes, spleen cells, or immune lymphocytes had no influence on this rate of mortality. Further, it was found that the immunologic unresponsiveness of mice protected by homologous marrow extended to heterologous rat red cells. Activated isologous spleen cells or lymphocytes from preimmunized mice conferred adoptive immunity to rat erythrocytes when transferred to lethally irradiated mice “saved” by isologous or homologous marrow. These data indicate that if donor-grafted cells still persist 21 to 28 days after irradiation of the host, they do not effectively destroy the transferred isologous tissues. The studies of other investigators were reviewed in light of these results and it is concluded that the mechanism of immunologic unresponsiveness of irradiated animals protected by foreign cells is not the same as “immunologic tolerance.” Since the data do not indicate a graft vs. host reaction, and cannot be interpreted exclusively as a host vs. graft reaction, an alternate hypothesis that a host vs. host reaction may be operative at times is suggested.