Immunobiology and privilege of neuronal retina and pigment epithelium transplants

Streilein, J. Wayne; Ma, Naili; Wenkel, Hartmut; Ng, Tat Fong; Zamiri, Parisa

doi:10.1016/s0042-6989(01)00185-7

Cited by 163 publications

(119 citation statements)

References 13 publications

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“…Placement of allogeneic tissue into the anterior chamber of the eye results in a protective response called anterior chamber-associated immune deviation (ACAID). 33 Similar immune deviation could be occurring in retinal implant recipients, which could explain graft survival despite the presence of HLA-mismatched graft antigens. If regulatory T cells are developing in response to retinal implants, they are not inhibiting memory B-cell antibody production as all antibody specificities, donor directed and non-donor specific, persisted in all sensitized patients studied here.…”

mentioning

confidence: 96%

“…33 Lack of apparent cell-mediated rejection of the retinal tissue implanted to the subretinal space likely derives from this immunologic protection. 33 Additionally, the absence of detectable graft damage from donor-specific antibodies that were present in some patients before implantation would indicate that the blood-brain barrier is prohibiting antibody infiltration into the subretinal space. Placement of allogeneic tissue into the anterior chamber of the eye results in a protective response called anterior chamber-associated immune deviation (ACAID).…”

mentioning

confidence: 99%

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Vision Improvement in Retinal Degeneration Patients by Implantation of Retina Together with Retinal Pigment Epithelium

Radtke

Aramant

Petry

et al. 2008

American Journal of Ophthalmology

226

191

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mentioning

confidence: 96%

mentioning

confidence: 99%

Vision Improvement in Retinal Degeneration Patients by Implantation of Retina Together with Retinal Pigment Epithelium

Radtke

Aramant

Petry

et al. 2008

American Journal of Ophthalmology

226

191

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“…Previous studies have shown that the retinal pigment epithelium (RPE) 4 monolayer functions as an immune-privileged tissue (4), and that RPE cells are the principal mediators of immune privilege in the subretinal space (5,6). Ocular pigment epithelium cells, either as explanted tissues or cultured cells, have been found to be immunosuppressive in vitro (7)(8)(9)(10)(11)(12)(13).…”

mentioning

confidence: 99%

Retinal Pigment Epithelium-Derived CTLA-2α Induces TGFβ-Producing T Regulatory Cells

Sugita

Horie

Nakamura

et al. 2008

The Journal of Immunology

106

124

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T cells that encounter ocular pigment epithelium in vitro are inhibited from undergoing TCR-triggered activation, and instead acquire the capacity to suppress the activation of bystander T cells. Because retinal pigment epithelial (RPE) cells suppress T cell activation by releasing soluble inhibitory factors, we studied whether soluble factors also promote the generation of T regulatory (Treg) cells. We found that RPE converted CD4+ T cells into Treg cells by producing and secreting CTLA-2α, a cathepsin L (CathL) inhibitor. Mouse rCTLA-2α converted CD4+ T cells into Treg cells in vitro, and CTLA-2α small interfering RNA-transfected RPE cells failed to induce the Treg generation. RPE CTLA-2α induced CD4+CD25+Foxp3+ Treg cells that produced TGFβ in vitro. Moreover, CTLA-2α produced by RPE cells inhibited CathL activity in the T cells, and losing CathL activity led to differentiation to Treg cells in some populations of CD4+ T cells. In addition, T cells in the presence of CathL inhibitor increased the expression of Foxp3. The CTLA-2α effect on Treg cell induction occurred through TGFβ signaling, because CTLA-2α promoted activation of TGFβ in the eye. These results show that immunosuppressive factors derived from RPE cells participate in T cell suppression. The results are compatible with the hypothesis that the eye-derived Treg cells acquire functions that participate in the establishment of immune tolerance in the posterior segment of the eye.

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“…It may suggest a more ''fitting niche'' of that region for tumor growth, or expression of certain chemoattractants as well as adhesion molecules and/or chemokines in that region, or protection from host immune responses. Indeed, the SRS in the retina has been shown a ''immunoprivileged site'' for tumors or allogeneic transplants (34). We intend to investigate the mechanism(s) of this phenomenon and this mouse model seems very applicable.…”

Section: Discussionmentioning

confidence: 99%

Eradication of Tumor Colonization and Invasion by a B Cell–Specific Immunotoxin in a Murine Model for Human Primary Intraocular Lymphoma

Mahesh

Shen

et al. 2006

Cancer Research

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Human primary intraocular lymphoma (PIOL) is predominantly a B cell-originated malignant disease with no appropriate animal models and effective therapies available. This study aimed to establish a mouse model to closely mimic human B-cell PIOL and to test the therapeutic potential of a recently developed immunotoxin targeting human B-cell lymphomas. Human B-cell lymphoma cells were intravitreally injected into severe combined immunodeficient mice. The resemblance of this tumor model to human PIOL was examined by fundoscopy, histopathology, immunohistochemistry, and evaluated for molecular markers. The therapeutic effectiveness of immunotoxin HA22 was tested by injecting the drug intravitreally. Results showed that the murine model resembles human PIOL closely. Pathologic examination revealed that the tumor cells initially colonized on the retinal surface, followed by infiltrating through the retinal layers, expanding preferentially in the subretinal space, and eventually penetrating through the retinal pigment epithelium into the choroid. Several putative molecular markers for human PIOL were expressed in vivo in this model. Tumor metastasis into the central nervous system was also observed. A single intravitreal injection of immunotoxin HA22 after the establishment of the PIOL resulted in complete regression of the tumor. This is the first report of a murine model that closely mimics human B-cell PIOL. This model may be a valuable tool in understanding the molecular pathogenesis of human PIOL and for the evaluation of new therapeutic approaches. The results of B cell-specific immunotoxin therapy may have clinical implications in treating human PIOL. (Cancer Res 2006; 66(21): 10586-93)

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Immunobiology and privilege of neuronal retina and pigment epithelium transplants

Cited by 163 publications

References 13 publications

Vision Improvement in Retinal Degeneration Patients by Implantation of Retina Together with Retinal Pigment Epithelium

Vision Improvement in Retinal Degeneration Patients by Implantation of Retina Together with Retinal Pigment Epithelium

Retinal Pigment Epithelium-Derived CTLA-2α Induces TGFβ-Producing T Regulatory Cells

Eradication of Tumor Colonization and Invasion by a B Cell–Specific Immunotoxin in a Murine Model for Human Primary Intraocular Lymphoma

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