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Discontinuous albumin density gradients were used to obtain enrichment of hemopoietic stem cells and depletion of T lymphocytes in aspirated dog bone marrow. Colony forming units in agar CFUCwere determined to evaluate the degree of enrichment achieved. An average CFUC concentration factor of 12.4 was obtained. All transplantations in the study were carried out between DLAidentical sibling combinations. The number of CFUC administered varied from 0.2 to 5.5×105kg and the number of nucleated cells transfused varied from 0.1 to 1.0×108kg.

An attempt is made to define the importance of non-SD (serologically defined) and non-LD (lymphocyte-defined) antigens in kidney allograft survival in nonimmunosuppressed dogs. In beagles, graft survival is prolonged by SD and LD matching in littermate donor-recipient pairs, but to a lesser extent in similarly matched nonlittermate donor-recipient combinations.

Significant prolongation of survival of nonrelated DLA-mis-matched renal allografts has been obtained in beagle recipients receiving three blood transfusions from nonrelated donors prior to kidney transplantation and immunosuppression after transplantation. Nontransfused DLA-identical or DLA 1 haplotype-different littermates of the transfused dogs were used as controls. Lymphocytotoxic antibodies were formed after the blood transfusions. A quantitative immune reactivity score correlated with graft survival. Low scores prior to transplantation were found in five transfused dogs that did not reject their allografts. High scores prior to transplantation were found in four animals rejecting their graft and in one dog that survived after an abortive rejection episode. The great similarities between the results obtained in this animal model and the observations made in human transplant patients indicate that this model can be utilized for a further analysis of the possibilities of blood transfusions in protecting subsequent renal allografts from immunological rejection.

The relationships between immune reactivity after blood transfusions, subsequent kidney allograft survival, and donor selection were studied in dogs. Animals with a high as well as low serological immune reactivity toward antigens contained in blood transfusion were observed.

A single transfusion of 200 ml of donor blood 14 days before renal transplantation in prospectively DL-A tissue typed beagle littermates appeared to have an effect on graft survival. Seventeen per cent of the recipients did respond to the transfusion with formation of lymphocytotoxic and haemagglutinating antibodies. These “responder dogs” rejected kidney grafts in an accelerated way, compared with the “nonresponders” and with the nontreated control dogs. Responsiveness appeared to occur in pairs of littermates, which suggests that responding potency is genetically determined. There was histological evidence of acute arteritis in the renal grafts of responders, whereas cell-mediated rejection was noted in nonresponders.

Recent data stress the importance of matching donor and recipient of an organ graft for both the serologically defined (SD) and lymphocyte-defined (LD) determinants. To allow experimental evaluation of the effect of these SD and LD structures in a noninbred experimental animal, mixed leukocyte culture tests were performed between SD identical and nonidentical dogs to clarify the LD system in these animals. The results of these experiments can be summarized as follows: (a) In the dog there is a LD locus distinct from the known SD loci, which in all probability is localized outside the first (SD-1) series locus on the chromosome. (b) The crossing-over frequency between the SD and LD loci on the chromosome is low. (c) Studies in SD identical unrelated dogs and random unrelated dogs show an apparent high linkage disequilibrium between SD and LD loci. (d) The LD system in dogs is polymorphic.

The major histocompatibility system of the dog (DL-A) was studied in more detail by immunogenetical methods. Suggestive evidence for the existence of two closely linked DL-A(sub)loci was found. The definition of three alleles at the first sublocus was clear for both mongrel and beagle populations. Three additional specificities appear to recognize antigens of a second sublocus, at least in the beagle colony. Differences in the frequency of the described specificities were shown between the mongrel and the beagle populations.