Dual effect of ciliary body cells on T lymphocyte proliferation

Helbig, Horst; Gurley, Rebecca C.; Palestine, Alan G.; Nussenblatt, Robert B.; Caspi, Rachel R

doi:10.1002/eji.1830201115

Cited by 35 publications

(10 citation statements)

References 28 publications

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“…Several groups have investigated the capacity of RPE cells to function as antigen-presenting cells and also as modulators of T-cell activation. Furthermore, it has been found that human RPE cells can induce apoptosis among activated T cells through a FAS/FASLG process [52]. Thus, RPE cells can both modulate eye colour and be involved in immune activation through the FAS/FASLG system, supporting a possible interaction between polymorphisms in the FAS and FASLG genes and known risk factors for CMM.…”

Section: Discussionmentioning

confidence: 98%

Polymorphisms of the FAS and FAS ligand genes associated with risk of cutaneous malignant melanoma

Larson

Zhang

et al. 2006

Pharmacogenetics and Genomics

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The FAS/FAS ligand (FASLG) system has a key role in regulating cell growth and thus tumorigenesis. Functional promoter polymorphisms of the FAS and FASLG genes alter the transcriptional activities, but no published study has investigated the role of these polymorphisms in the etiology of cutaneous malignant melanoma (CMM). In a hospital-based, case-control study of 602 non-Hispanic white CMM patients and 603 cancer-free age- and sex-matched control subjects, we genotyped FAS-1377G>A, FAS-670A>G, FASLG-844T>C and FASLG-IVS2nt-124G>A polymorphisms and assessed their respective associations with CMM risk. We found that an increased risk of CMM was associated with the FAS-1377GG [adjusted odds ratio (OR)=1.32; 95% confidence interval (CI)=1.00-1.75 for -1377GG] and -670AA (adjusted OR=1.28; 95% CI=1.00-1.65 for -670AA) genotypes compared to the -1377AA/AG and -670AG/GG genotypes, respectively; an increased risk of CMM was associated with the FASLG-IVS2nt-124AG+GG (OR=1.54; 95% CI=1.18-2.01) genotype compared to the AA genotype, but no evident risk was associated with any of the FAS-844T>C genotypes. In the combined analysis of these four variant alleles, we found that, compared to those having 0-3 variants, those having 4-8 variant alleles had a significantly increased risk for CMM (OR=1.38; 95% CI=1.10-1.73), and this risk was more pronounced in subgroups of old (>50 years) males, and those who were at low risk of sunlight-induced CMM, except for having fair skin colour, moles, dysplastic nevi and a family history of cancer. In conclusion, genetic variants in the FAS and FASLG genes may contribute to the etiology of CMM in the general population, particularly in those with a low risk of sunlight-induced CMM.

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Section: Discussionmentioning

confidence: 98%

Polymorphisms of the FAS and FAS ligand genes associated with risk of cutaneous malignant melanoma

Larson

Zhang

et al. 2006

Pharmacogenetics and Genomics

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“…The parenchymal cells in the eye, including the retinal glial Müller cells [37], cells from rat ciliary bodies [38], and astrocytes [39], have been reported to have an immune regulatory effect. We [6,8] and others [5, 7, 30, 40 -43] have previously shown that RPE cells can promote or inhibit T cell activation.…”

Section: Discussionmentioning

confidence: 99%

PD-L1hi retinal pigment epithelium (RPE) cells elicited by inflammatory cytokines induce regulatory activity in uveitogenic T cells

Sun

Jiang

et al. 2010

Journal of Leukocyte Biology

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We previously reported that after exposure to inflammatory cytokines, such as IL-17 and IFN-γ, RPE cells express increased amounts of suppressor of cytokine signaling, leading to general suppression of the inflammatory response. Here, we demonstrate that RPE cells expressed increased levels of PD-L1 in response to IL-17, IFN-γ, or Poly I:C. These PD-L1(hi) RPE cells inhibited the pathogenic activities of IRBP-specific T cells, which usually induced uveitis when injected into naïve mice (EAU). The suppressed pathogenicity of these uveitogenic T cells after exposure to PD-L1(hi) RPE cells could be partially reversed by anti-PD-L1 antibodies. Nevertheless, IRBP-specific T cells pre-exposed to PD-L1(hi) RPE cells displayed substantial suppressor activity, which strongly inhibited the activation of fresh IRBP-Teffs in response to subsequent antigenic challenge and when transferred into naïve mice, inhibited the induction of EAU by IRBP-Teff transfer. These findings suggest that inflammatory cytokine-triggered up-regulation of PD-L1 on RPE constitutes a critical factor for inducing infiltrated uveitogenic T cells with regulatory activities, which may accelerate the natural resolution of T cell-mediated intraocular inflammation.

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“…The aqueous humor factors also prevent antigen-presenting cells (APC) from presenting antigen in a manner that induces Th1 cell activation [3]. In addition, the immunosuppressive mechanisms of the ocular microenvironment include contactdependent suppression of T cell activation by iris, ciliary body, and retinal pigmented epithelial cells [4][5][6] along with the extensive expression of FasL to induce apoptosis in activated Th1 cells [7,8].…”

Section: Introductionmentioning

confidence: 99%

Inducible immune regulation following autoimmune disease in the immune-privileged eye

Kitaichi

Namba

Taylor

2005

Journal of Leukocyte Biology

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The immune-privileged eye has the potential to induce regulatory immunity along with local mechanisms of immunosuppression. Rodent models of human autoimmune uveoretinitis [experimental autoimmune uveoretinitis (EAU)] recover without spontaneous recurrence of uveitis, which differs from uveitis in some humans. This raises the possibility that the mechanism of immune privilege in the rodent eye can reimpose itself during autoimmune uveoretinitis and re-establish tolerance to autoantigen. To investigate this possibility, we examined the spleens of EAU-recovered mice for regulatory immunity. We detected regulatory immunity when we adoptively transferred post-EAU spleen cells into other mice immunized for EAU. We could not detect this regulatory immunity in enucleated mice nor in naive mice. Moreover, unlike the mechanisms of anterior chamber-associated immune deviation, the suppression was only mediated by post-EAU CD4 + T cells, which required activation with autoantigen presented by post-EAU spleen antigen-presenting cells (APC). Our results demonstrate that when the immune-privileged ocular microenvironment recovers from an autoimmune response, it has influenced systemic immunity to retinal autoantigen by affecting APC and mediating induction of potential regulatory CD4 + T cells laying in wait in the post-EAU spleen for restimulation.

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Dual effect of ciliary body cells on T lymphocyte proliferation

Cited by 35 publications

References 28 publications

Polymorphisms of the FAS and FAS ligand genes associated with risk of cutaneous malignant melanoma

Polymorphisms of the FAS and FAS ligand genes associated with risk of cutaneous malignant melanoma

PD-L1hi retinal pigment epithelium (RPE) cells elicited by inflammatory cytokines induce regulatory activity in uveitogenic T cells

Inducible immune regulation following autoimmune disease in the immune-privileged eye

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