Generation of Regulatory T Cells to Antigen Expressed in the Retina

McPherson, Scott W.; Heuss, Neal D.; Lehman, Ute; Gregerson, Dale S.

doi:10.2174/157339511796196584

Cited by 6 publications

(7 citation statements)

References 43 publications

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“…However, the double Tg mice had a reduced delayed-type hypersensitivity (DTH) response to βgal compared to βgalTCR mice. In total, our results suggested that the down regulation of immune responses associated with retinal βgal was due the generation of Ag-specific CD4 + CD25 + Tregs from naïve CD4 + precursors and was dependent on the presence of retinal βgal (34–37). To promote analysis of the nature of retinal Ag-specific Tregs the model was moved onto the B6 background.…”

Section: Resultsmentioning

confidence: 76%

“…However, recent studies have shown that iTregs induced to tissue-specific self-Ag can regulate Teffs (32, 33). Similarly, we have used Tg mice expressing E. coli beta-galactosidase (βgal, arrβgal mice) in retina photoreceptor cells in conjunction with T cell receptor (TCR)-Tg mice specific for βgal to demonstrate that a consistent outcome of retinal βgal expression is a down regulation of systemic immune responses to βgal that is, in part, due to the induction of Tregs from naïve, peripheral βgal-specific CD4 + cells (34–37). …”

Section: Introductionmentioning

confidence: 99%

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Local “On-Demand” Generation and Function of Antigen-Specific Foxp3+ Regulatory T Cells

McPherson

Heuss

Gregerson

2013

The Journal of Immunology

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Extrathymically derived regulatory T cells (iTregs) protect against autoimmunity to tissue-specific antigens (Ag). However, whether Ag-specific iTreg generation and function is limited to secondary lymphoid tissue or whether it can occur within the tissue-specific, local environment of the cognate Ag remains unresolved. Mice expressing beta-galactosidase (βgal) on a retina specific promoter (βgal mice) in conjunction with mice expressing green fluorescent protein (GFP) and diphtheria toxin (DTx) receptor (DTR) under control of the FoxP3 promoter, and βgal-specific T cell receptor transgenic (BG2) mice were used to examine this question. Local depletion (ocular DTx), but not systemic depletion (intra-peritoneal DTx), of βgal-specific iTregs enhanced experimental autoimmune uveoretinitis induced by activated βgal-specific effector T cells. Injections of small amounts of βgal into the anterior chamber of the eye produced similar numbers of βgal-specific iTregs in the retina whether or not the mouse was depleted of pre-existing, circulating Tregs. Together these results suggest that protection from tissue-specific autoimmunity depends on the function of local Ag-specific iTregs, and that the retina is capable of local, “on-demand” iTreg generation that is independent of circulating Tregs.

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Section: Resultsmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Local “On-Demand” Generation and Function of Antigen-Specific Foxp3+ Regulatory T Cells

McPherson

Heuss

Gregerson

2013

The Journal of Immunology

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“…This finding is in agreement with previous reports that described expression of recoverin and a small number of other retinal antigens in mouse and human thymus, where the formation of natural regulatory T cells (nTreg) is known to occur in response to self-antigen exposure ( 23 , 24 ). In addition, inducible regulatory T cells (iTreg) may also be generated and supported by expression of recoverin and other retinal antigens by the retina itself ( 25 , 26 ). Recoverin-specific nTreg or iTreg cells in the retina would be expected to provide local protection from immune attack by secreting IL-10, and possibly expression of other immune regulatory factors in response to presentation of recoverin peptides by local antigen presenting cells ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

T Helper 1 Cellular Immunity Toward Recoverin Is Enhanced in Patients With Active Autoimmune Retinopathy

et al. 2018

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Autoimmune retinopathy (AIR) causes rapidly progressive vision loss that is treatable but often is confused with other forms of retinal degeneration including retinitis pigmentosa (RP). Measurement of anti-retinal antibodies (ARA) by Western blot is a commonly used laboratory assay that supports the diagnosis yet does not reflect current disease activity. To search for better diagnostic indicators, this study was designed to compare immune biomarkers and responses toward the retinal protein, recoverin, between newly diagnosed AIR patients, slow progressing RP patients and healthy controls. All individuals had measurable anti-recoverin IgG and IgM antibodies by ELISA regardless of disease status or Western blot results. Many AIR patients had elevated anti-recoverin IgG1 levels and a strong cellular response toward recoverin dominated by IFNγ. RP patients and controls responded to recoverin with a lower IFNγ response that was balanced by IL-10 production. Both AIR and RP patients displayed lower levels of total peripheral blood mononuclear cells that were due to reductions of CD4+ TH cells. A comparison of messenger RNA (mRNA) for immune-related genes in whole blood of AIR patients versus RP patients or controls indicated lower expression of ATG5 and PTPN22 and higher expression of several genes involved in TH cell signaling/transcription and adhesion. These data indicate that an immune response toward recoverin is normal in humans, but that in AIR patients the balance shifts dramatically toward higher IFNγ production and cellular activation.

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“…Retina-specific Treg cells are produced in response to antigens found in the retina. These can either be natural Tregs, which are generated against retinal antigens expressed in the thymus, or these can be generated independently of thymus from mature peripheral T cells based on exposure to antigens ( 103 ). In the retina, this cell population has been associated with uveoretinitis, where an increased number of CD4 + CD25 + Tregs was detected in spleen and eye ( 104 ).…”

Section: Protector or Promoter: Regulatory T Cellsmentioning

confidence: 99%

Cellular Stress Response and Immune Signaling in Retinal Ischemia–Reperfusion Injury

2016

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Ischemia–reperfusion injury is a well-known pathological hallmark associated with diabetic retinopathy, glaucoma, and other related retinopathies that ultimately can lead to visual impairment and vision loss. Retinal ischemia pathogenesis involves a cascade of detrimental events that include energy failure, excitotoxic damage, calcium imbalance, oxidative stress, and eventually cell death. Retina for a long time has been known to be an immune privileged site; however, recent investigations reveal that retina, as well as the central nervous system, elicits immunological responses during various stress cues. Stress condition, such as reperfusion of blood supply post-ischemia results in the sequestration of different immune cells, inflammatory mediators including cytokines, chemokines, etc., to the ischemic region, which in turn facilitates induction of inflammatory conditions in these tissues. The immunological activation during injury or stress per se is beneficial for repair and maintenance of cellular homeostasis, but whether the associated inflammation is good or bad, during ischemia–reperfusion injury, hitherto remains to be explored. Keeping all these notions in mind, the current review tries to address the immune response and host stress response mechanisms involved in ischemia–reperfusion injury with the focus on the retina.

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Generation of Regulatory T Cells to Antigen Expressed in the Retina

Cited by 6 publications

References 43 publications

Local “On-Demand” Generation and Function of Antigen-Specific Foxp3+ Regulatory T Cells

Local “On-Demand” Generation and Function of Antigen-Specific Foxp3+ Regulatory T Cells

T Helper 1 Cellular Immunity Toward Recoverin Is Enhanced in Patients With Active Autoimmune Retinopathy

Cellular Stress Response and Immune Signaling in Retinal Ischemia–Reperfusion Injury

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