Histocompatibility Studies in a Closely Bred Colony of Dogs

Abstract

The DL-A system of histocompatibility plays an important role in conditioning the survival of cardiac allografts in the unmodified canine host. The mean survival time of six cardiac allografts performed in DL-A-compatible littermate dogs obtained from a closely bred colony of beagles was 53.2 days, while the MST of transplants performed in seven DL-A-incompatible animals was 7.3 days. The MST of cardiac allografts performed in nine DL-A-compatible nonlittermate beagles was 26.3 days, as compared with 6.3 days in six DL-A-incompatible nonlittermate transplants. The results did not appear to be affected by Swisher erythrocyte-group incompatibilities. The MST of 28 cardiac allografts performed in randomly selected mongrel dogs was 10.0 days. Incompatibilities for DL-A antigens e, f, g, l, and m may constitute major barriers to transplantation, but antigens b, c, d, and k appeared to act as weak histocompatibility antigens. Under controlled conditions of donor-recipient DL-A compatibility, cardiac allografts may be less immunogenic than renal transplants. Heart transplants performed across major donor-recipient DL-A incompatibilities appeared, however, to be more vulnerable to the events of allograft rejection than renal allografts performed under similar conditions. The selection of optimally compatible donor-recipient combinations for organ transplantation may be aided materially by genetic studies of the transmission of DL-A antigens to the animals under consideration.

Histocompatibility Studies in a Closely Bred Colony of Dogs

“…Recipients.--The results of transplantation of skin, kidney, heart, and fiver allografts in the Cooperstown Colony have been reported in part previously (19)(20)(21). In order to permit a more precise assessment of the comparative immunogenicity of these organs, the results were correlated in the present study with the DL-A genotypes of donors and recipients.…”

“…Previous observations have indicated that progress in the application of tissue-typing techniques to the selection of optimally compatible organ transplant donor-recipient pairs in the Cooperstown Colony was dependent upon a further genetic definition of the DL-A system in this colony (20). Such genetic studies were considered to be of particular importance to the assessment of the comparative immunogenicity of the major transplantable organs in the canine species.…”

“…Although significant prolongations in allogralt survival have been shown to occur in the Cooperstown Colony under conditions of DL-A compatibility (17)(18)(19)(20)(21), the results have also suggested the need for further genetic and serological studies of the antigenic components of the DL-A system. Further progress in the selection of donorrecipient combinations which would predictably be associated with long-term organ transplant survival appeared to be particularly dependent upon genetic studies of the transmission of the DL-A antigens within this particular canine colony (20).…”

“…These observations, taken together with evidence that the leukocyte antigens detected in the Cooperstown Colony behave as mendelian autosomal dominants (21), suggested that such antigens were components of a major system of histocompatibility, for which the term DL-A was proposed in 1969 (20). The studies of Bos et al (22), Westbroek et al (23), Chandler et al (24), and Blumenstock and associates (25) have provided further evidence to support the existence of such a major histocompatibility locus in the canine species.…”

“…Further progress in the selection of donorrecipient combinations which would predictably be associated with long-term organ transplant survival appeared to be particularly dependent upon genetic studies of the transmission of the DL-A antigens within this particular canine colony (20). This type of analysis also appeared to be a prerequisite for an assessment of the comparative immunogenicity of the major transplantable organs under defined conditions of DL-A compatibility.…”