Histocompatibility Studies in a Closely Bred Colony of Dogs

Rapaport, Felix T.; Hanaoka, Takao; Shimada, Tsutomu; Cannon, Frances D.; Ferrebee, Joseph W.

doi:10.1084/jem.131.5.881

Cited by 34 publications

(13 citation statements)

References 19 publications

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“…The correlations noted between serologically determined and genetically confirmed states of donor-recipient compatibility and the survival of skin, kidney, heart, and liver allografts are in keeping with the concept that the DL-A system is the principal system of histocompatibility in the canine species (19). The longest allograft survivals occurred under conditions of DL-A genetic and serological identify (Table V) ; transplants performed between littermates bearing different sets of parental haplotypes were accorded the shortest survivals in this category of animals.…”

Section: Discussionmentioning

confidence: 59%

“…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.…”

Section: Transplantation Techniques; Correlation Of Th~ Results With mentioning

confidence: 99%

“…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).…”

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confidence: 99%

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Histocompatibility Studies in a Closely Bred Colony of Dogs

Dausset

Rapaport

Cannon

et al. 1971

The Journal of Experimental Medicine

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The segregation of the canine DL-A leukocyte group antigen(s) b, c, d, e, f, g, h, k, l, and m has been traced in 141 consecutive matings in the Cooperstown Colony of beagles. All of the leukocyte antigen(s) were regularly transmitted en bloc from parent to offspring, with no instance of independent segregation. A total of 23 haplotypes, including six different DL-A antigen patterns (gl, bkhfm, bkcd, e, be, fgl) was observed. 31 different DL-A phenotypes were observed in a population of 100 mongrel dogs. A number of statistically significant positive and negative associations between individual DL-A antigenic components occurred in this population. The results support the concept of the DL-A system as a complex immunogenetic system governed by a single region (or locus) of an autosomal pair of chromosomes. Studies of skin, kidney, heart, and liver allografts in the Cooperstown Colony indicated that the longest allograft survivals occur under genetically and serologically defined conditions of donor-recipient DL-A compatibility. Skin and renal allografts generally behaved in parallel fashion, while cardiac allografts survived for longer periods of time (MST = 47.1 days) than kidneys (MST = 28.1 days) or skin (MST = 25.1 days) under conditions of DL-A identity. Heart transplants were rejected at a more rapid rate than kidney, however, in DL-A-incompatible donor-recipient combinations. Liver transplants were accorded the longest survival time (MST = 76.2 days) under conditions of DL-A identity, but were rejected at a rapid rate (MST = 5 days) in DL-A-incompatible nonlittermate donor-recipient pairs. The results provide further evidence that the DL-A system is the principal system of histocompatibility in the canine species. The differences in survival of different organs under similar conditions of donor-recipient DL-A compatibility suggest, however, the existence of a number of unknown variables which may also be capable of significantly affecting allograft behavior.

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Section: Discussionmentioning

confidence: 59%

Section: Transplantation Techniques; Correlation Of Th~ Results With mentioning

confidence: 99%

mentioning

confidence: 99%

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Histocompatibility Studies in a Closely Bred Colony of Dogs

Dausset

Rapaport

Cannon

et al. 1971

The Journal of Experimental Medicine

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“…The numbers opposite to these haplotypes in the last column of this detail previously (19). All recipients underwenit removal of their own kidneys within 29-54 (lays after renal transplantation.…”

Section: Miethodsmentioning

confidence: 99%

Induction of Allogeneic Unresponsiveness in Adult Dogs

Rapaport¹,

Bachvaroff²,

Watanabe³

et al. 1978

J. Clin. Invest.

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A B S T R A C T Exposure to supralethal total body irradiation and transplantation of bone marrow from a DLA-and pedigree-identical donor have regularly produced successful engraftment and the establishment of stable long-term chimerism in beagles of the Cooperstown colony. Bone marrow allografts performed in pairs of dogs bearing identical DLA haplotypes derived from different pedigree origins (i.e., different classes of the same haplotype) yielded two different results. Depending upon the particular haplotype pedigree combination lused, such transplants either led to long-term chimerisnm or to failures of engraftmenit, secondary disease, anid death of the recipients (i.e., pedigree-incompatible combinations).Radiation chimeras given bone marrow from a DLAand pedigree-identical donor were challenged within 8-12 h after marrow transplantation with a renal allograft obtained from another DLA-and pedigree-identical donor. The recipients have remained unresponsive to such renal allografts and have sturvived indefinitely with normal renial f'unction. In These results highlight the potential importance of genetically controlled histocompatibility determinants other than DLA in conditioning allograft reactivity. The determinants uncovered in the present study appear to be linked to the DLA complex, as demonstrated by the ability of the pedigree origins of DLA haplotypes present in individual dogs to serve as an effective marker system for such non-DLA antigen(s). The restults also point to the potential usefulness of the early postirradiation period for the induction of allogenieic uinresponsiveness in large adult mammals. INTRODUCTIONThe selectively bred lines of' beagles miainitainied at The Mary Imogene Bassett Hospital in Cooperstowni, N. Y., have provided an animal resouirce in which the transplantation of' bonie marrow from genotypically DLA-idenitical donors into irradiated littermate and(or) nonlittermate dogs bearing DLA haplotypes derived from the same pedigree origins can regularly produce long-term stable chimerism, with no evidence of a graftversus-host response at any time after transplantation (1-5). Challenge of'the recipients with kidney (1), heart (6), lung (7), liver (8, 9), pancreas (8, 9), or skin (3) It is the purpose of this report to present a series of studies aimed at providing ftirther insight into the role of genetically determined histocompatibility factors in affecting the outcome of transplantation in the canine species. A continuing series of bone marrow allografts in the Cooperstown colony between DLA-identical donor-recipienit coml)inations bearing the same pedigree origins is used as the basic reference standard. The data are compared with the ouitcome of bone marrow allografts in pairs of animals which bear the same DLA haplotypes, but where such haplotypes were inherited from different pedigree sources. In the latter instaniee, some pedigree combinations have produced long-term stable chimerisnm, while certain other pairings have resulted regularly in failures of engraftnment or...

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“…In an extension of the elegant studies of Epstein et al (34), Rubinstein and associates (35), and Mollen et al (36) produced a battery of typing sera capable of detecting 10 different leukocyte antigen specificities (or sets of specificities) in the Cooperstown colony of beagles. Transplantation studies performed on the basis of donor-recipient compatibility for these antigens in the Cooperstown Cclony have shown that allografts of skill (36), kidney (37), heart (38), lung (39), and liver (40) are accorded prolonged survivals in compatible animals. Conversely, allografts transplanted across major leukocyte group incompatibilities are rejected rapidly.…”

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Histocompatibility Studies in a Closely Bred Colony of Dogs

Rapaport

Watanabe

Cannon

et al. 1972

The Journal of Experimental Medicine

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17 Cooperstown beagles of known DL-A genotypes were exposed to supralethal total body irradiation and received a bone marrow allograft from a DL-A-identical donor; 11 littermate and 6 nonlittermate donor-recipient pairs were studied. The recipients are surviving uneventfully for 315, 364, 424, 440, 531, 531, 584, 605, 625, 635, and 649 days in the littermate group and for 211, 279, 280, 368, 479, and 480 days in the nonlittermate group. The radiation chimeras underwent bilateral nephrectomy and received a kidney allograft obtained from their respective marrow donor within 43–120 days after bone marrow transplantation. The renal allografts are surviving for 191, 200, 221, 234, 313, 349, 361, 377, 378, 405, 441, 444, 482, 557, 580, 581, and 586 days, respectively. 12 of 13 skin allografts obtained from the marrow donor are at present surviving in the recipients for 107, 110, 110, 110, 116, 122, 128, 143, 143, 162, 178, and 199 days, respectively; one graft was rejected at 84 days. In contrast, the radiation chimeras rejected 25 skin allografts obtained from DL-A-incompatible donors within 10.5–21 days (MST = 15.2 days). Skin transplants obtained from DL-A-identical siblings of the bone marrow donors were rejected within 20–36 days (MST = 25.8 days) in recipients of bone marrow cells obtained from littermate donors. Recipients of nonlittermate bone marrow transplants accorded such allografts a prolonged survival time of 27–76 days (MST = 56.2 days). Prospective selection of genotypically DL-A-identical donor-recipient pairs results in the regularly reproducible long-term survival of bone marrow allografts. The radiation chimeras produced in this manner have developed a donor-specific state of unresponsiveness to kidney and skin allografts. The results are consistent with the existence in the canine species of at least three closely linked genetic systems relevant to transplantation, including DL-A, MLC, and a possible bone marrow transplantation locus.

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Histocompatibility Studies in a Closely Bred Colony of Dogs

Cited by 34 publications

References 19 publications

Histocompatibility Studies in a Closely Bred Colony of Dogs

Histocompatibility Studies in a Closely Bred Colony of Dogs

Induction of Allogeneic Unresponsiveness in Adult Dogs

Histocompatibility Studies in a Closely Bred Colony of Dogs

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