Histocompatibility Studies in a Closely Bred Colony of Dogs

Rapaport, Felix T.; Watanabe, Kôji; Cannon, Frances D.; Mollen, N; Blumenstock, David A.; Ferrebee, Joseph W.

doi:10.1084/jem.136.5.1080

Cited by 31 publications

(24 citation statements)

References 54 publications

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“…In contrast, skin grafts from other sources, inclutd(inig donors bearing the same DLA haplotypes, derived from the saime pedigree origins as the recipienit, were rejected at a rate similar to that observed in uniitreated anlilimals (3).…”

Section: Introductionmentioning

confidence: 86%

“…The method of supralethal total body irradiation has been described previously (3). Briefly, each recipient was exposed to 1,200-1,400 R of continuous irradiation from two opposing 60Co sources, at a source-to-target distance of 2-2.5 m, with an exposure rate of 3-4 R/min.…”

Section: Miethodsmentioning

confidence: 99%

“…Challenge of'the recipients with kidney (1), heart (6), lung (7), liver (8,9), pancreas (8,9), or skin (3) allografts obtained from the donor of marrow within [3][4][5][6] mo after irradiation and marrow reconstitution has demonstrated, in addition, that such chimeras are unresponsive to other allogeneic tissues obtained from that particular donor. The individual specificity of this state of tolerance was shown by the ability of the chimeras to reject skinl grafts from other DLA-identical and(or) DLA-incompatible sources at a rate siimilar to that docuimented in uintreated dogs (3).…”

Section: Introductionmentioning

confidence: 99%

“…The 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)(2)(3)(4)(5). Challenge of'the recipients with kidney (1), heart (6), lung (7), liver (8,9), pancreas (8,9), or skin (3) allografts obtained from the donor of marrow within [3][4][5][6] mo after irradiation and marrow reconstitution has demonstrated, in addition, that such chimeras are unresponsive to other allogeneic tissues obtained from that particular donor.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 86%

Section: Miethodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Induction of Allogeneic Unresponsiveness in Adult Dogs

Rapaport¹,

Bachvaroff²,

Watanabe³

et al. 1978

J. Clin. Invest.

Self Cite

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“…Eight dogs (experimental group) were sensitized through skin transplantations as described by Rapaport et al [13]. After 14 days, the animals received a second skin transplantation from the same donor.…”

Section: Protocol and Experimental Modelmentioning

confidence: 99%

Humoral rejection after heart transplantation: reliability of intramyocardial electrogram recordings (IMEG) and myocardial biopsy

et al. 1997

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In recent years, as the importance of humoral-mediated rejection has increasingly become recognized, the fact that endomyocardial biopsies (BX) evaluated according to the criteria of the International Society for Heart and Lung Transplantation often produce false-negative results has become a matter of concern. To evaluate the reliability of measuring intramyocardial ECG amplitude (IMEG) and immunofluorescence evaluation (FITC-labeled anti-IgG/ IgM staining) of endomyocardial biopsies (IFM), heterotopic neckheart transplantation (HTX) was performed on eight beagles previously sensitized through skin transplantations. After HTX, IMEG, echo, and donor-specific antibodies in serum (IgG, IgM) were determined daily and myocardial biopsies (IFM, BX) were performed once every 2 days. Accelerated (humoral) rejection occurred on the 5th (4th-5th) postoperative day and sensitivity of IMEG, IFM, and BX was 100 YO, 75 %, and 12.5 %, respectively. In each case rejection was recognized so early that it was possible to initiate therapy with "restitutio ad integrum". Our results show that, as opposed to endomyocardial biopsy (IFM, BX), IMEG diagnosis detected humoralmediated rejection early and with high reliability.

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The requirement of intrathymic mixed chimerism and clonal deletion for a long‐lasting skin allograft tolerance in cyclophosphamide‐induced tolerance

et al. 1990

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Mechanisms of cyclophosphamide (CY)-induced tolerance were studied. When C3H/He Slc (C3H; H-2k, Mls-1b) mice were primed i.v. with 1 x 10(8) viable spleen cells from H-2-identical AKR/J Sea (AKR; H-2k, Mls-1a) mice and treated with 200 mg/kg of CY 2 days later, a long-lasting skin allograft tolerance to AKR was established. When [C57BL/6 Sea (B6; H-2b, Mls-1b) x AKR]F1 (B6AKF1) cells were used as the tolerogen, however, only a moderate, but not long-lasting, skin tolerance to AKR was observed. In the C3H mice treated with AKR cells and CY, the intrathymic clonal deletion of V beta 6+ T cells, which are strongly correlated with reactivity to Mls-1a antigens, was observed in the chimeric thymus on day 35, although neither the clonal deletion of V beta 6-bearing T cells nor the mixed chimerism was observed in the thymus on day 14. In the C3H mice treated with B6AFKF1 cells followed by CY, however, neither the clonal deletion of V beta 6+ T cells nor the mixed chimerism was observed in the thymus throughout the test period. In the lymph nodes of the C3H mice treated with AKR cells and CY, only CD4+ V beta 6+ T cells, bur not CD8+V beta 6+ T cells, had selectively decreased by day 14, and they were hardly detectable on day 35. The selective decrease of CD4+V beta 6+ T cells in the lymph nodes was also observed by day 14 when B6AKF1 cells were used as the tolerogen, although CD4+V beta 6+ T cells gradually increased on day 35, at which time almost all skin grafts from AKR had already been rejected. These results strongly support the necessity of the intrathymic mixed chimerism and clonal deletion of donor-reactive T cells for a long-lasting skin allograft tolerance in CY-induced tolerance.

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Histocompatibility Studies in a Closely Bred Colony of Dogs

Cited by 31 publications

References 54 publications

Induction of Allogeneic Unresponsiveness in Adult Dogs

Induction of Allogeneic Unresponsiveness in Adult Dogs

Humoral rejection after heart transplantation: reliability of intramyocardial electrogram recordings (IMEG) and myocardial biopsy

The requirement of intrathymic mixed chimerism and clonal deletion for a long‐lasting skin allograft tolerance in cyclophosphamide‐induced tolerance

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