The graft versus host reaction (GVHR), which results from the injection of parental strain spleen cells beneath the kidney capsule of F1 hybrid rats, is transferable during its developmental phase into F1 hybrid hosts isogeneic with the primary host, but not into secondary hosts of the parental (donor) strain. Furthermore, the GVHR propagates but rarely in secondary hybrid hosts which are allogeneic with respect to the primary hosts, but which are also genetically tolerant of donor-type cells. These findings indicate that the donor cells not only initiate the GVHR but also maintain it by virtue of immunologically specific activity.

Whole-body irradiation of (LBf)F1 and (LBN)F1 hosts 24 hours prior to the injection of parental (L) spleen cells results in inhibition of the subsequent GVHR to a degree commensurate with the radiation damage sustained by the lymphoid system of the host. Furthermore, propagation of transferred GVHRs did not occur if susceptible secondary hybrid hosts had been previously irradiated. These findings indicate that radiosensitive host cells play a continuing and essential role in the pathogenesis of the invasive-destructive lesion. It is concluded that the development of this lesion depends upon the continuous interaction of the specifically reactive donor-type cells with an immunologically non-specific population of host mononuclears.

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