Cytogenetic studies of RFM mice which are susceptible to host versus graft disease following the perinatal inoculations of (T6 × RFM)F1 spleen cells and of T6T6 mice which are not

Abstract Experimental host versus graft (HVG) syndrome is the fatal complex of lesions which results from perinatal inoculations of F 1 hybrid spleen cells into certain related parental strains of mice. It is primarily an incuded T-cell immunodeficiency syndrome with B-cell hyperplasia and hyperfunction. In this study, quantitative cytogenetic studies were done on the spleens and lymph nodes of young RFM mice which developed HVG diseas following the perinatal inoculations of (T 6 × RFM)F 1 spleen cells, and on T 6 T 6 and irradiated RFM mice which received similar inoculations, but did not develop the disease. RFM host susceptibility was associated with the engraftment of low numbers (12%) of donor F 1 cells in their spleens. Healthy T 6 T 6 chimeras had 25% donor cells in their spleens, and long-lived RFM chimeras, in which HVG disease had been prevented by irradiation, had 48% donor F 1 cells in their spleens. The finding of comparably high proportions of F 1 cells in the nodes of 25-day-old diseased RFM mice (87%) and healthy T 6 T 6 chimeras (79%) further supported the idea that the spleen was the major site of RFM host resistance. These studies associate susceptibility to lethal HVG disease with host resistance to the perinatal induction of tolerance to semiallogenic cells. Past and present work show that HVG disease can be prevented by the successful induction of tolerance in susceptible hosts by overwhelming or suppressing their resistance. As yet, there is no evidence that F 1 versus parent reactivity plays a pathogenic role.