MHC expression in fragment and full-thickness allogeneic embryonic retinal transplants

Ghosh, Fredrik; Larsson, Jörgen; Wilke, K.

doi:10.1007/s004170000138

Cited by 9 publications

(18 citation statements)

References 30 publications

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“…Further, we have previously found MHC up-regulation in allogeneic fragmented transplanted cells, but not in fullthickness counterparts (Ghosh et al 2000). Taken together our present results and previous studies suggest that retinal elements in the donor tissue up-regulate MHC molecules in response to fragmentation trauma, and that the ensuing inflammation is a rejection caused by the immunological disparity between donor and host.…”

Section: Discussionsupporting

confidence: 84%

“…Studies on donor tissue characteristics in relation to graft survival include donor-age, inclusion of antigen presenting cells and blood vessels, but as yet, tissue-integrity has not been extensively explored (Aramant et al, 1988;Marion et al, 1990). We have previously reported that allogeneic fragmented grafts (rabbit-to-rabbit) induce up-regulation of major histocompatibility complex (MHC) class I and II molecules in the graft and host while their full-thickness counterparts do not show such upregulation (Ghosh et al, 2000). We have further reported that full-thickness donor tissue, at least in the short-term, can survive xenogeneic transplantation between discordant species (rat-to-rabbit) without immunosuppression (Rauer and Ghosh, 2001).…”

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confidence: 99%

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Neuroretinal xenotransplantation to immunocompetent hosts in a discordant species combination

2008

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In spite of its immune privileged state, xenotransplantation within the CNS is associated with rapid graft destruction in immunocompetent hosts. Efforts to enhance graft survival have mostly focused on host immune response, whereas relatively little attention has been paid to donor tissue characteristics. In the present paper, we explore long-term survival of xenogeneic full-thickness neuroretinal transplants in immunocompetent hosts and investigate the significance of tissue integrity in relation to graft survival.Adult rabbits receiving no immunosuppression were used as hosts and fetal Sprague-Dowley rat neuroretina as donors. Using vitreoretinal surgical techniques, rabbits received either a full thickness or a fragmented neuroretinal graft to the subretinal space of one eye. Eyes receiving full-thickness grafts were examined morphologically after 91 days and fragmented grafts after 7-14 days.Surviving full thickness grafts were found in 6 out of 8 eyes, 4 of which displayed the normal laminated appearance. Major Histocompatibility Complex (MHC) up-regulation in surviving grafts was minimal and they contained a well organized photoreceptor layer, Protein Kinase C (PKC) labeled rod bipolar cells, parvalbumin labeled AII amacrine cells and glial fibrillary acidic protein (GFAP) labeled Müller cells. Fragmented grafts (n=6) were all destroyed or showed severe signs of rejection. A mass of inflammatory cells derived from the choroid was evident in these specimens, and no labeling of retina-specific cells were seen.We conclude that full-thickness rat neuroretina can survive for several months after subretinal transplantation to the subretinal space of immunocompetent rabbits, while fragmented counterparts are rapidly rejected. Surviving full-thickness grafts can develop many of the normal retinal morphological characteristics, indicating a thriving relationship between the initially immature donor tissue and its foreign host. Our results strongly indicates that donor tissue integrity is a crucial factor for graft survival in CNS xenotransplantation.

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Section: Discussionsupporting

confidence: 84%

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confidence: 99%

Neuroretinal xenotransplantation to immunocompetent hosts in a discordant species combination

2008

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“…If we add to this the possibility of enhanced exposure of conventional transplantation and retina-restricted antigens in fragmented donor tissue, acute rejection of such grafts is hardly surprising [6]. In accordance with our earlier reports on transplantation to the SRS [11,16], donor tissue integrity appears to be an important factor for survival of neuroretinal grafts also in non-immune privileged sites.…”

Section: Discussionsupporting

confidence: 78%

“…Primary antibodies directed against microtubule-associated protein 2 (MAP2, monoclonal, mouse IgG1 isotype, 1:200 dilution, Sigma, St. Louis, MO, USA) and glial fibrillary acidic protein (GFAP, monoclonal, 1:1000 dilution, Chemicon International, Temecula, CA, USA) were used to detect graft-related neurons, and glial cells, respectively [14,15]. To identify inflammatory cells, a monoclonal antibody raised against rabbit major histocompatibility complex (MHC) class II was used (Mab 45-3, 1:200 dilution, Spring Valley Laboratories, Woodbine, Md., USA) [16]. Labeled sections were kept at room temperature for 20 min and then rinsed three times for 5 min in a solution of PBS and 0.25% Triton X-100 at 7.2 pH.…”

Section: Tissue Preparationmentioning

confidence: 99%

Immune privilege of allogeneic neuroretinal transplants in the subconjunctival space

Ghosh

Rauer

Arnér

2008

Graefes Arch Clin Exp Ophthalmol

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Allogeneic fetal full-thickness neuroretinal transplants can survive for several weeks in a non-immune privileged environment in which adult grafts are rapidly rejected. Fetal grafts gradually shrink, lose their architecture and go through a glial transformation accompanied by low-grade inflammation. The rabbit neuroretina thus appears to enjoy partial immune privilege, the extent of which depends on the development state of the tissue. The characterization of neuroretinal immune privilege will hopefully influence future clinical trials of retinal transplantation.

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“…HLA-ABC molecules are expressed on the RPE constitutively. HLA-ABC molecules and HLA-DR molecule are upregulated significantly after being stimulated with proinflammatory cytokines such as IFN-γ and TNF-α [12]. The ICAM-1 molecule is the ligand for the LFA-1 on T cells.…”

Section: Discussionmentioning

confidence: 99%

Culture in vitro Modulation of Human Leukocyte Antigen Molecules and Costimulatory Molecules on Human Retinal Pigment Epithelium

Xie

2007

Ophthalmologica

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Purpose: To determine the potential of culture in vitro to alter the human leukocyte antigen (HLA) molecules and costimulatory molecules on human retinal pigment epithelium (RPE). Methods: Pure RPE were isolated and cultured. Two sets of RPE (normal and activated) were used. Activated RPE were obtained by incubating primary cultures of RPE with recombinant human interferon-γ. The expression of HLA molecules and costimulatory molecules on human RPE at different passages after culture in vitro were analyzed quantitatively by flow cytometry. Results: In the process of routine culture on culture flask, the duration of culture in vitro was significantly correlated with the expression of HLA-ABC molecules on the normal RPE and the activated RPE (r = –0.893, p < 0.001 and r = –0.964, p < 0.001 respectively), HLA-DR molecule on the activated RPE (r = –0.901, p < 0.001) and intercellular adhesion molecule-1 on the normal RPE (r = 0.961, p < 0.001). There were no correlations between the duration of culture in vitro andthe expression of HLA-DR molecule on the normal RPE, intercellular adhesion molecule-1 on the activated RPE, B7-1 and B7-2 molecules on the normal RPE and the activated RPE. Conclusions: The chronic rejection is the major immunological rejection following RPE allogeneic graft. Culture in vitro modulation of HLA molecules and costimulatory molecules on RPE may increase lymphocyte infiltration and activation and promote the chronic rejection following allograft RPE transplantation.

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MHC expression in fragment and full-thickness allogeneic embryonic retinal transplants

Cited by 9 publications

References 30 publications

Neuroretinal xenotransplantation to immunocompetent hosts in a discordant species combination

Neuroretinal xenotransplantation to immunocompetent hosts in a discordant species combination

Immune privilege of allogeneic neuroretinal transplants in the subconjunctival space

Culture in vitro Modulation of Human Leukocyte Antigen Molecules and Costimulatory Molecules on Human Retinal Pigment Epithelium

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