Antigen-specific accumulation of naïve, memory and effector CD4 T cells during anterior uveitis monitored by intravital microscopy

Dullforce, Per; Seitz, Greg W.; Garman, Kiera L.; Michael, Julie A.; Crespo, Sergio M.; Fleischman, Ross J.; Planck, Stephen R.; Parker, David C.

doi:10.1016/j.cellimm.2006.03.005

Cited by 18 publications

(21 citation statements)

References 42 publications

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“…To avoid the consequences of this inflammation, the eye employs an extensive array of mechanisms through which innate and adaptive immune effectors can be regulated. To study severe uveitis disorders in humans, the experimental autoimmune uveitis (EAU) 3 animal model has been developed. EAU is a T cell-mediated autoimmune disease that leads to the destruction of the neural retina and related tissues, including serous retinal detachment, retinal folding, photoreceptor damages, vasculitis, retinitis and vitreitis, and, ultimately, blindness (1-3).…”

mentioning

confidence: 99%

“…EAU is a T cell-mediated autoimmune disease that leads to the destruction of the neural retina and related tissues, including serous retinal detachment, retinal folding, photoreceptor damages, vasculitis, retinitis and vitreitis, and, ultimately, blindness (1-3). Initiation of the major pathogenic events in EAU occurs by activating effector T cells that then react with retinal Ags such as interphotoreceptor retinoid-binding proteins (IRBP) (3). The activated effector T cells have an increased ability to enter target organs.…”

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confidence: 99%

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Acquisition of T Regulatory Function in Cathepsin L-Inhibited T Cells by Eye-Derived CTLA-2α during Inflammatory Conditions

Sugita

Horie

Nakamura

et al. 2009

The Journal of Immunology

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Pigment epithelium isolated from the eye possesses immunosuppressive properties such as regulatory T (Treg) cell induction; e.g., cultured retinal pigment epithelium (RPE) converts CD4+ T cells into Treg cells in vitro. RPE constitutively expresses a novel immunosuppressive factor, CTLA-2α, which is a cathepsin L (CathL) inhibitor, and this molecule acts via RPE to induce Treg cells. To clarify CTLA-2α’s role in the T cell response to RPE in ocular inflammation, we used the experimental autoimmune uveitis (EAU) animal model to examine this new immunosuppressive property of RPE. In EAU models, TGF-β, but not IFN-γ inflammatory cytokines, promotes the up-regulation of the expression of CTLA-2α in RPE. Similarly, CTLA-2α via RPE was able to promote TGF-β production by the CD4+ T cells. The RPE-exposed T cells (RPE-induced Treg cells) greatly produced TGF-β and suppressed bystander effector T cells. There was less expression of CathL by the RPE-exposed T cells, and CathL-inhibited T cells were able to acquire the Treg phenotype. Moreover, CathL-deficient mice spontaneously produced Treg cells, with the increase in T cells potentially providing protection against ocular inflammation. More importantly, CD4+ T cells from EAU in CathL knockout mice or rCTLA-2α from EAU animals were found to contain a high population of forkhead box p3+ T cells. In both EAU models, there was significant suppression of the ocular inflammation. These results indicate that RPE secretes CTLA-2α, thereby enabling the bystander T cells to be converted into Treg cells via TGF-β promotion.

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confidence: 99%

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confidence: 99%

Acquisition of T Regulatory Function in Cathepsin L-Inhibited T Cells by Eye-Derived CTLA-2α during Inflammatory Conditions

Sugita

Horie

Nakamura

et al. 2009

The Journal of Immunology

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“…We have previously reported that these cells include both dendritic cells and macrophages [23], though Camelo et al found uptake of soluble dextran to occur predominantly by macrophages in rat iris [24] An antigen-specific accumulation of CD4+ T cells occurs after OVA or OVA+LPS injection into the eyes of mice that have previously received an intravenous injection of DO11.10 CD4+ T cells (Dullforce et al [17] and Figure 1B). Significantly more labeled DO11.10 cells are found in the iris of eyes 24 hours after injection with OVA+LPS than with HSA+LPS ( Figure 1B) or BSA+LPS (data not shown).…”

Section: Resultsmentioning

confidence: 90%

“…We have recently described techniques to label APCs within the iris with fluorescent antigen [16] and we have developed a model of T cell-mediated, antigen-specific inflammation within the iris [17]. Combining these two capabilities has allowed us to characterize the interaction between T cells and APCs in this model of anterior uveitis.…”

Section: Introductionmentioning

confidence: 99%

T cell–antigen-presenting cell interactions visualized in vivo in a model of antigen-specific inflammation

Rosenbaum

Ronick

Song

et al. 2008

Clinical Immunology

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Videomicroscopy is being used increasingly to characterize the interaction of T cells and antigenpresenting cells (APCs) within lymphatic tissues but has not been reported, to our knowledge, at sites of inflammation. We employed intravital videomicroscopy to study an anterior uveitis model using DO11.10 T cells and ovalbumin (OVA). T cell movement in iris was consistent with a random walk independent of the presence of recognized antigen and had a lateral speed slower than T cells in lymph node. Lingering of T cells adjacent to APCs suggested that they were physically interacting. This apparent contact demonstrated antigen specificity when comparing results from DO11.10 cells with OVA versus bovine serum albumin (BSA) loaded APCs but not when comparing results from OVA-loaded APCs with DO11.10 versus HA clonotype 6.5 T cells. Further studies with this model system should clarify the contribution of T cell-APC communication at a site of inflammation, infection, or immunization.

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“…26 The codes of uveitis and Herpes zoster are both related to immunologic factors. [27][28][29] In one study, performed after the Kobe earthquake, a increase in uveitis after the disaster was seen that was administered to psychological stress due to the disaster. 30 However, we have no explanation for this finding even though immunologic changes after disasters were described.…”

Section: Discussionmentioning

confidence: 99%

Health Problems Presented to Family Practices in The Netherlands 1 Year Before and 1 Year After a Disaster

Soeteman¹,

Yzermans²,

Kerssens³

et al. 2007

The Journal of the American Board of Family Medicine

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Background: Disasters often have negative health consequences. Studies of health problems presented in family practice before and after a disaster are rare. The present study analyzed health problems before and after a disaster and predictors of increased morbidity after the disaster as presented in family practice.Methods: A matched cohort study design with measurements 1 year before the disaster and 1 year after the disaster. Victims (N ‫؍‬ 9183) and matched controls (N ‫؍‬ 7066) were surveyed in the electronic medical records of 30 family practices after the explosions of a fireworks depot in The Netherlands. All health problems were registered using the International Classification of Primary Care.Results: Victims showed significantly higher prevalence rates for psychological problems after the disaster than before the disaster (422 vs133 per 1000 person-years; P < .001) and for problems of the musculoskeletal system (450 vs 401 per 1000 person-years; P < .05).Relocation because of the disaster (odds ratio, 10.65; 95% confidence interval, 8.15-13.94) and, to a lesser degree, psychological morbidity before the disaster (odds ratio, 2.31; 95% confidence interval, 1.42-3.76) were the strongest predictors of psychological problems after the disaster.

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Antigen-specific accumulation of naïve, memory and effector CD4 T cells during anterior uveitis monitored by intravital microscopy

Cited by 18 publications

References 42 publications

Acquisition of T Regulatory Function in Cathepsin L-Inhibited T Cells by Eye-Derived CTLA-2α during Inflammatory Conditions

Acquisition of T Regulatory Function in Cathepsin L-Inhibited T Cells by Eye-Derived CTLA-2α during Inflammatory Conditions

T cell–antigen-presenting cell interactions visualized in vivo in a model of antigen-specific inflammation

Health Problems Presented to Family Practices in The Netherlands 1 Year Before and 1 Year After a Disaster

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