Cell-mediated cytotoxicity to DLA and non-DLA antigens measured by a microcytotoxicity assay in dog families

Abstract

The microcytotoxicity assay (MA) can detect cell-mediated cytotoxicity (CMC) to alloantigens. To assess whether the CMC observed in the MA segregates in concordance with genes linked or not to the major histocompatibility complex, studies were performed in three dog families. Recipients were sensitized by skin graft and blood transfusion from either DLA-identical or haploidentical littermates. Lymphocytes obtained sequentially before and after were reacted to cultured skin fibroblasts from the recipient, the donor, the other littermates, and the parents. In most cases grafting was followed by specific positive CMC against the donor, regardless of the DLA compatibility or of graft survival time. No CMC was noted before allograft or after autograft. Segregation studies showed that approximately 80% of CMC reactions after DLA incompatible sensitization were concordant with DLA. After DLA compatible immunization the pattern of cytotoxicity failed to segregate with DLA, and most of the reactions were able to distinguish between targets of identical sibs. In these cases. cytotoxic lymphocytes against at least the donor reacted against cells from either or both parents, while when no killing of the donors' targets occurred, no CMC could be detected in the family. CMC was not linked to sex difference. No DLA restriction of its expression was observed. These data indicate that after in vivo immunization the MA may be detecting genetically transmitted alloantigens coded for by genes not linked to DLA.