Graft Versus Host Reactions. Their Natural History, and Applicability as Tools of Research

Simonsen, Morten

doi:10.1159/000391332

Cited by 221 publications

(135 citation statements)

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“…As Simonsen has pointed out, the successful transfer of a GVHR into a second F1 hybrid, which is isogeneic with the primary host, constitutes solid evidence for the continuing reactivity of the original donor component against host antigens (1).…”

Section: Resultsmentioning

confidence: 98%

The Interaction of Donor and Host Lymphoid Cells in the Pathogenesis of Renal Cortical Destruction Induced by a Local Graft Versus Host Reaction

Elkins¹

1966

The Journal of Experimental Medicine

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The graft versus host reaction (GVHR), which results from the injection of parental strain spleen cells beneath the kidney capsule of F1 hybrid rats, is transferable during its developmental phase into F1 hybrid hosts isogeneic with the primary host, but not into secondary hosts of the parental (donor) strain. Furthermore, the GVHR propagates but rarely in secondary hybrid hosts which are allogeneic with respect to the primary hosts, but which are also genetically tolerant of donor-type cells. These findings indicate that the donor cells not only initiate the GVHR but also maintain it by virtue of immunologically specific activity. Whole-body irradiation of (LBf)F1 and (LBN)F1 hosts 24 hours prior to the injection of parental (L) spleen cells results in inhibition of the subsequent GVHR to a degree commensurate with the radiation damage sustained by the lymphoid system of the host. Furthermore, propagation of transferred GVHRs did not occur if susceptible secondary hybrid hosts had been previously irradiated. These findings indicate that radiosensitive host cells play a continuing and essential role in the pathogenesis of the invasive-destructive lesion. It is concluded that the development of this lesion depends upon the continuous interaction of the specifically reactive donor-type cells with an immunologically non-specific population of host mononuclears.

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Section: Resultsmentioning

confidence: 98%

The Interaction of Donor and Host Lymphoid Cells in the Pathogenesis of Renal Cortical Destruction Induced by a Local Graft Versus Host Reaction

Elkins¹

1966

The Journal of Experimental Medicine

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Section: Bone Marrow Transplantationmentioning

confidence: 99%

“…The alternative possibility that donor and recipient immunecell populations coexisted in neonatally tolerant animals in a mutually nonreactive state while retaining the ability to function collaboratively (e.g. in a joint immune response to infection) was abandoned when no direct experimental support could be found 10 it has since been learned that the outcome in the neonatal tolerance model is highly variable and that a state approaching permanent clonal deletion is uncommon 11 . Recently, it has been shown that the ability of donor-derived leukocyte subsets to proliferate in response to a skin graft challenge was a more critical determinant of neonatal tolerance outcome than the baseline level of chimerism 12 .…”

mentioning

confidence: 99%

The lost chord: microchimerism and allograft survival

et al. 1996

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Recent evidence suggests that passenger leukocytes migrate after organ transplantation and produce persistent chimerism, which is essential for sustained survival of the allografts. Here, Thomas Starzl and colleagues argure that this hematolymphopoietic chimerism provides an important framework for the interpretation of basic and therapeutically oriented transplantataion research.Medawar's characterization of rejection 1 as a host-versus-graft (HVG) reaction (Fig. 1a) was the cornerstone of transplantation immunology. A decade later, this concept was transposed in the context of a graft-versus-host (GVH) reaction (Fig. 1b), in which histoincompatible hematolymphopoietic grafts rejected the immunologically defenseless recipients 2,3 . The resulting assumption that allograft acceptance or rejection could be understood by studying HVG or GVH immunologic responses in isolation led to prompt acceptance of the one-way in vitro tests of immune reactivity as 'minitransplant' surrogates. However, this assumption did not provide a blanket explanation for observations made in animal and human allograft recipients. The one-way paradigmUntil 1959, preparatory donor leukocyte infusion into cytoablated organ recipients was an expected natural extension of the neonatal tolerance model of Billingham, Brent and Medawar 4 and its adult cytoablation analogues 3 . However, when long-term survival of human kidney allografts was accomplished in a few sublethally irradiated recipients without donor leukocyte infusion, and then regularly without cytoreduction under continuous pharmacologic immunosuppression, the need either for chimerism or host preconditioning lost favor.The identification of 'passenger leukocytes' as the primary antigenic component of organs 6,7 led to the belief that their destruction by the host immune system was essential for organ engraftment. When these cells were found to be migratory 8 , including dendritic cells (DCs) 9 , their sensitization effects and presumed elimination at peripheral and intragraft sites was taken for granted. Bone marrow transplantationMajor histocompatibility complex (MHC)-restricted models of acquired tolerance were widely considered to have validated Burnet's prediction that developing lymphocytes could be purged of self-reactive cells before they achieved functional maturity, even following bone marrow transplantation. The alternative possibility that donor and recipient immunecell populations coexisted in neonatally tolerant animals in a mutually nonreactive state while retaining the ability to function collaboratively (e.g. in a joint immune response to infection) was abandoned when no direct experimental support could be found 10 it has since been learned that the outcome in the neonatal tolerance model is highly variable and that a state approaching permanent clonal deletion is uncommon 11 . Recently, it has been shown that the ability of donor-derived leukocyte subsets to proliferate in response to a skin graft challenge was a more critical determinant of neonatal tole...

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“…It is well established that an essential condition for the development of systemic graft-vs.-host reactions, such as runt or transplantation disease, in addition to well-studied local manifestations of graft-vs.-host reactivity, such as splenomegaly, hepatomegaly, and local renal lesions, is that the putative attacking donor lymphoid cells must be confronted by alien antigens determined by the H-2 locus, or its equivalent in other species (23)(24)(25). However, if these cells are provided by a specifically presensitized donor, graft-vs.-host reactions are capable of developing in the absence of a difference at the major locus.…”

Section: Discussionmentioning

confidence: 99%

An Analysis of the Genetic Requirements for Delayed Cutaneous Hypersensitivity Reactions to Transplantation Antigens in Mice

Streilein

Billingham

1970

The Journal of Experimental Medicine

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The experiments reported herein provide ample evidence that mice, like most other mammalian species, are capable of displaying readily observable and reproducible delayed cutaneous hypersensitivity reactions indicative of transplantation immunity. By employing a variety of genetically defined strains, it has been shown that a genetic requirement for the development of a positive normal lymphocyte transfer reaction in mice is a difference between host and cell donor at the H-2 locus. By contrast, the immune lymphocyte transfer reaction consistently reflected the full range of histoincompatibility, both inclusive and exclusive of the H-2. It was incidentally discovered that erythema regularly accompanied delayed cutaneous reactions in the skins of female mice, whereas no local redness accompanied their counterparts in male skins. The influence of cutaneous erythema on the scoring of delayed skin reactions is discussed.

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Graft Versus Host Reactions. Their Natural History, and Applicability as Tools of Research

Cited by 221 publications

References 0 publications

The Interaction of Donor and Host Lymphoid Cells in the Pathogenesis of Renal Cortical Destruction Induced by a Local Graft Versus Host Reaction

The Interaction of Donor and Host Lymphoid Cells in the Pathogenesis of Renal Cortical Destruction Induced by a Local Graft Versus Host Reaction

The lost chord: microchimerism and allograft survival

An Analysis of the Genetic Requirements for Delayed Cutaneous Hypersensitivity Reactions to Transplantation Antigens in Mice

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