Graft Rejection in a Congenic Panel of Rats With Defined Immune Response Genes for Class I Antigens

Stewart, Robert L.; Stephenson, Paula; Godden, Urma; Butcher, G. A.; Roser, Bruce

doi:10.1097/00007890-198510000-00017

Cited by 5 publications

(4 citation statements)

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“…In all strains, the ensuing local destruction of host myofibers was followed by normal regeneration. These studies indicate, as in transplantation studies of other tissues, that "low" and "high" responder rodent strains exist (Butcher and Howard, 1982;Stewart et al, 1985;Sprent et al, 1986;Rosenberg et al, 1987;Ilano et al, 1989) that mount an immune response with different time courses.…”

Section: Fate Of Allogeneic Myoblast Transplants Without Lmmunosupprementioning

confidence: 85%

“…Other studies have noted strain differences in the efficiency of immunosuppressive treatments in rodents (Ilano et al, 1989) leading to the concept of low and high responder strains in different experimental paradigms of transplant immunology. Elucidation of the cellular and molecular bases for such genetic differences (Butcher and Howard, 1982;Stewart et al, 1985;Sprent et al, 1986;Rosenberg et al, 1987;llano et al, 1989) may contribute to an understanding of human variabilities in response to immunosuppressive drugs.…”

Section: Discussionmentioning

confidence: 99%

“…The immune response to purified antigens and organ transplants as well as the efficacy of immunosuppressive treatments can vary significantly among rodent strains (Butcher and Howard, 1982;Stewart et al, 1985;Sprent et al, 1986;Rosenberg et al, 1987;Ilano et al, 1989). As a control for subsequent studies of transient immunosuppression, the time course of allogeneic myoblast rejection in different strains of mice was first established.…”

Section: Fate Of Allogeneic Myoblast Transplants Without Lmmunosuppression In Different Host Strainsmentioning

confidence: 99%

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Transient immunosuppressive treatment leads to long-term retention of allogeneic myoblasts in hybrid myofibers.

Pavlath

Rando

Blau

1994

The Journal of Cell Biology

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Abstract.Normal and genetically engineered skeletal muscle cells (myoblasts) show promise as drug delivery vehicles and as therapeutic agents for treating muscle degeneration in muscular dystrophies. A limitation to the widespread use of myoblast transplantation is the immune response of the host to the transplanted cells. Allogeneic myoblasts are rapidly rejected unless immunosuppressants are administered. However, continuous immunosuppression is associated with significant toxic side effects. Here we test whether immunosuppressive treatment, administered only transiently after allogeneic myoblast transplantation, allows the long-term survival of the transplanted cells in mice. Two immunosuppressive treatments with different modes of action were used: (a) cyclosporine A (CSA); and (b) monoclonal antibodies to intracellular adhesion molecule-1 and leukocyte function-associated molecule-1. The use of myoblasts genetically engineered to express fl-galactosidase allowed quantitation of the survival of allogeneic myoblasts at different times after cessation of the immunosuppressive treatments. Without host immunosuppression, allogeneic myoblasts were rejected from all host strains tested, although the relative time course differed as expected for low and high responder strains. The aUogeneic myoblasts initially fused with host myofibers, but these hybrid cells were later destroyed by the massive immunological response of the host. However, transient immunosuppressive treatment prevented the hybrid myofiber destruction and led to their long-term retention. Even four months after the cessation of treatment, the hybrid myofibers persisted and no inflammatory infiltrate was present in the tissue. Such long-term survival indicates that transient immunosuppression may greatly increase the utility of myoblast transplantation as a therapeutic approach to the treatment of muscle and nonmuscle disease.

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Section: Fate Of Allogeneic Myoblast Transplants Without Lmmunosupprementioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Fate Of Allogeneic Myoblast Transplants Without Lmmunosuppression In Different Host Strainsmentioning

confidence: 99%

See 1 more Smart Citation

Transient immunosuppressive treatment leads to long-term retention of allogeneic myoblasts in hybrid myofibers.

Pavlath

Rando

Blau

1994

The Journal of Cell Biology

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“…The role of MHC class I and class II antigens in the survival of vascularized allografts both in mice and rats has been studied using congenic and recombinant strains of experimental animals. [1][2][3][4][5][6] The results however, have been controversial, mainly because of the poor compatibility of the donor and recipient strains. In addition, the immunomodulatory function of soluble MHC class I proteins, has been uncertain.…”

Section: Introductionmentioning

confidence: 99%

Impact of donor MHC class I or class II antigen deficiency on first‐ and second‐set rejection of mouse heart or liver allografts

Shen

et al. 1996

Immunology

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SUMMARYThe influence of donor major histocompatibility complex (MHC) class I-or class II-deficiency on the initiation of first-and second-set rejection of mouse heart and liver allografts was examined. C3H (H-2 k ) mice received heterotopic cardiac or orthotopic liver grafts from unmodified B10 (H-2 b ), B6 (H-2 b ), b2m (H-2 b ; class I deficient) or AB 0 (H-2 b ; class II deficient) donors. Organ survival was also investigated in C3H recipients that had been presensitized by a normal B10 skin graft 2-3 weeks before heart or liver transplantation. The absence of cell surface MHC class I or class II resulted in significant prolongation of primary cardiac allograft survival. Three of seven (43%) MHC class I-deficient, and two of five (40%) class II-deficient heart grafts were accepted indefinitely (survival time >100 days). Thus both MHC class I and class II molecules appear to be important for the elicitation of first-set rejection in the heart allograft model. All liver allografts survived >100 days in normal recipients. In C3H recipients that had been presensitized by a B10 skin graft, however, both heart and liver grafts from AB 0 (class II deficient) donors underwent accelerated rejection (median survival time [MST] 3 and 4 days, respectively). In contrast, liver grafts from class I-deficient mice (b2m) were still accepted indefinitely by B10 skin-presensitized C3H recipients, whereas class I-deficient hearts survived significantly longer than those from class II-deficient or normal donors. These data demonstrate that the expression of donor MHC class I, and not class II is crucial in initiating second-set organ allograft rejection. In vitro monitoring revealed that at the time of organ transplant, both splenocytes and serum of the skinpresensitized animals displayed high cytotoxicity against AB 0 (class II-deficient) but not against b2m (class I-deficient) targets.

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Immunologic suppression mediated by genetically modified hepatocytes expressing secreted allo-MHC class I molecules

et al. 1998

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Graft Rejection in a Congenic Panel of Rats With Defined Immune Response Genes for Class I Antigens

Cited by 5 publications

References 0 publications

Transient immunosuppressive treatment leads to long-term retention of allogeneic myoblasts in hybrid myofibers.

Transient immunosuppressive treatment leads to long-term retention of allogeneic myoblasts in hybrid myofibers.

Impact of donor MHC class I or class II antigen deficiency on first‐ and second‐set rejection of mouse heart or liver allografts

Immunologic suppression mediated by genetically modified hepatocytes expressing secreted allo-MHC class I molecules

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