Cytotoxic Typing Antisera for Marrow Grafting in Littermate Dogs

Epstein, Robert B.; Storb, R; Ragde, Haakon; Thomas, E. Donnall

doi:10.1097/00007890-196801000-00005

Cited by 151 publications

(62 citation statements)

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“…The method of preparation of antisera and techniques for serological typing by the lymphocytotoxicity technique have been described in earlier reports (12,13 With the antisera currently in use in the Cooperstowvn colony, somiie haplotypes (represented symbolically in Table I as E, *, _, and V) appear to carry more than two SD specificities; one haplotype (A) carries three defined specificities, and so far, the haplotype represented as " " is detected by only one antigen. The superabundance of apparent antigenis on some haplotypes (e.g., 0, which appears to transmit no less than five SD antigenis) may be due to cross-reactivity or to the lack of ability to distiiiguish between public specificities which are comimiiloIn to several alleles and private specificities which have a very restricted distribution (10).…”

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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Section: Miethodsmentioning

confidence: 99%

Induction of Allogeneic Unresponsiveness in Adult Dogs

Rapaport¹,

Bachvaroff²,

Watanabe³

et al. 1978

J. Clin. Invest.

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“…The DL-A phenotypes and presumed genotypes of the donors and recipients used to produce these antisera are outfined in Table I. The technique of lymphocytotoxicity of Epstein et al (15) was employed, with removal of erythrocytes by sedimentation before nylon infiltration, in order to separate lymphocytes from polymorphonuclear leukocytes. Erythrocyte group antigens A, C, and D were detected with the typing sera and technique of Swisher (27).…”

Section: Source Of Experimental Animals Production Of Typing Sera Amentioning

confidence: 99%

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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“…In initial studies, serological histocompatibility typing with a small panel of lymphocytotoxic antisera was used to select canine donor-recipient pairs for grafting. Clearly, the degree of matching with these antisera appeared to be an important determinant of Received for publication 28 December 1970. marrow graft rejection, development of a lethal graftversus-host (GVH)1 disease or eventual survival of the recipient after infusion of allogeneic marrow (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%