Bone marrow transplantation across major histocompatibility barriers in rabbits. I. A positive role for graft-versus-host reactivity in engraftment.

The impact of graft-versus-host reactivity on the outcome of bone marrow transplantation (BMT) was analysed in rabbits of defined major histocompatibility (RLA) types by injecting 10(8) parental type cells into newborn F1 recipients. Distinctive allotypic determinants on immunoglobulin (Ig) molecules of donor and recipient rabbits provided markers for analysing B cell chimerism, while T cell chimerism was assessed by sex chromosome analysis. The characteristics of graft-versus-host disease (GVHD) in the rabbit were first analysed in a group of F1 recipients transplanted neonatally with spleen or lymph node cells of parental type. The majority of such animals died in the third to fifth week of life, while exhibiting clinical and histological signs of GVHD, i.e. profound anemia, pancytopenia, and lymphoid aplasia. Runting, as indicated by weight loss, was not observed. No surviving chimeras resulted from this group. In contrast, injection of 10(8) parental type bone marrow (BM) cells caused death from GVHD in only 27% of recipients. Thirty-two percent (7/22) became permanent chimeras, and engraftment failure was observed in the remainder. In BM chimeras T cells and B cells of donor origin were dominant or completely replaced cells of the recipient type. These differences from the results of transferring RLA-matched lymphoid cells suggest a significant role for GVH reactivity, with or without overt GVHD, in the establishment of permanent chimerism.