Peripheral Tolerance Via the Anterior Chamber of the Eye: Role of B Cells in MHC Class I and II Antigen Presentation

Ashour, Hossam M.; Niederkorn, Jérry Y.

doi:10.4049/jimmunol.176.10.5950

Cited by 52 publications

(79 citation statements)

References 41 publications

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“…ACAID APCs functionally resemble the eye-derived APCs, and are believed to induce T-cell regulation (10,11). ACAID T-cell regulation mediated via CD4+ and CD8+ Tregs could be tested by monitoring DTH responses in experimental mice (2,6). Thus, we examined the ability of in vitro-generated CIIspecific ACAID APCs to promote the induction of peripheral tolerance.…”

Section: Discussionmentioning

confidence: 99%

“…We used an in vitro spleen cell culture system that we had previously used to generate Tregs that express the same properties and surface markers as Tregs produced in vivo (2,6). ACAID APCs (5x 10 6 ) , specific to CII, were added to a 100 mm petri dish containing 5x 10 7 spleen cells harvested from normal Balb/c mice and the culture was incubated for 5-7 days at 37°C before testing for the presence ofTregs.…”

Section: In Vitro Generation Ofacaid Tregsmentioning

confidence: 99%

“…We have described details of the LAT assay previously (2,6,9). Briefly, the putative Tregs were injected (1x 10 (…”

Section: Local Adoptive Transfer (Lat) Assaymentioning

confidence: 99%

“…ACAID APCs were generated in vitro as described previously (2,6). Ocular-like APCs from Balb/c mice were generated as described before (12).…”

Section: Generation Ofacajd Apcsmentioning

confidence: 99%

“…Professional APCs can be immunogenic or tolerogenic depending on the involvement of unique cytokines that impact their maturation and activation, such as the immunosuppressive cytokines IL-I 0 and TGF-~that push towards the tolerogenic type (4,5). The in vitro culture of F4/80+ macrophages with antigens in the presence ofTGF-~2 could lead to the generation of ocular-like ACAID APCs, that induce antigen-specific immune tolerance when injected into experimental mice (2,6).…”

mentioning

confidence: 99%

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Thein vitro-Inductionof Type II Collagen-Specific Immune Tolerance in BALB/C Mice

Farooq

2013

Eur J Inflamm

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Type II collagen (CII) protein is the main component of hyaline cartilage. The clinical importance of CII in arthritis, aging, and osteoarthritis is significant, but its ability to induce specific immune tolerance has not been extensively studied previously. We have recently proven that CII is capable of inducing Anterior Chamber Associated Immune Deviation (ACAID) when injected into the eye. Here, we hypothesized that ACAID-mediated tolerance could be induced in Balb/c mice that receive an intravenous administration of CII-induced in vitro-generated ocular-like antigen-presenting cells (APCs) or T regulatory cells (Tregs), Delayed hypersensitivity (DTH) assays were used to examine this hypothesis. In mice injected with CII-specific ACAID APCs, the specific regulatory activities resided in the spleen cells, splenic T cells, and ACAID CD8+ T cells, as proven by local adoptive transfer (LAT) assays. Conversely, there was a lack of regulatory activity in the CD4+ CD25+ T cell compartment of the recipient mice. Thus, ACAID CD8+ Tregs generated in vitro could be directly responsible for the expression of CII-driven ACAID-mediated tolerance and could be used as potential therapeutic tools in the treatment of CII-associated autoimmune diseases.The eye is vulnerable to severe inflammatory immune responses that could cause serious damage. Thus, regulatory mechanisms are in place to protect against intra-ocular inflammation. Anterior chamber-associated immune deviation (ACAID) is one such mechanism whereby the antigenic entry into the AC induces potent antigen-specific immune tolerance that is not only localized in the eye but also extends to the periphery. In order to obtain this potent antigen-specific peripheral immune tolerance, ACAID involves intricate multicellular communications between the eye-derived F4/80+ antigen presenting cells (APCs), splenic T cells, marginal zone B cells, NKT cells, and yo T cells (l). ACAID is characterized by the negative regulation of systemic Th 1 responses and of delayed type hypersensitivity (DTH) responses (2). This is achieved through professional APCs that induce the generation of afferent and efferent T regulatory cells (Tregs) (3), which could potentially be used to curb T-helper cell responses in autoimmune diseases. Professional APCs can be immunogenic or tolerogenic depending on the involvement of unique cytokines that impact their maturation and activation, such as the immunosuppressive cytokines IL-I 0 and TGF-~that push towards the tolerogenic type (4, 5). The in vitro culture of F4/80+ macrophages with antigens in the presence ofTGF-~2 could lead to the

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Section: Discussionmentioning

confidence: 99%

Section: In Vitro Generation Ofacaid Tregsmentioning

confidence: 99%

“…We have described details of the LAT assay previously (2,6,9). Briefly, the putative Tregs were injected (1x 10 (…”

Section: Local Adoptive Transfer (Lat) Assaymentioning

confidence: 99%

“…ACAID APCs were generated in vitro as described previously (2,6). Ocular-like APCs from Balb/c mice were generated as described before (12).…”

Section: Generation Ofacajd Apcsmentioning

confidence: 99%

mentioning

confidence: 99%

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Thein vitro-Inductionof Type II Collagen-Specific Immune Tolerance in BALB/C Mice

Farooq

2013

Eur J Inflamm

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Innate responses of B cells

Gray

Barr

2007

Eur J Immunol

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In this review, we describe the non-antibody-mediated functions of B cells within the immune system. In addition to antibody production, B cells also present antigen to T cells, programme T cell differentiation and regulate effector T cell responses and much of this is mediated by the cytokines they make. We focus on the potential of B cells to perform these functions simply as a result of activation via 'innate' receptors (e.g. Tolllike receptors) and often independently of BCR ligation. We feel an appreciation of these broad and often antigen-nonspecific functions is important at a time when there is an increasing use of B cell depletion as a therapy for autoimmune disease.

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Peripheral CD4⁺T‐cell tolerance is induced in vivo by rare antigen‐bearing B cells in follicular, marginal zone, and B‐1 subsets

2013

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Summary B cells are efficient APCs when they internalize antigen via BCR-mediated uptake. Adoptively transferred antigen-presenting B cells can induce T-cell tolerance to foreign and self antigens; however, it is unknown whether endogenous B cells presenting self-peptides interact with naïve T cells and contribute to peripheral T-cell self-tolerance. Moreover, the relative abilities of mature B-cell subsets to induce T-cell tolerance have not been examined. To address these questions, we created a new mouse model wherein a very small fraction of B cells expresses an antigen transgene that cannot be transferred to other APCs. We limited antigen expression to follicular, marginal zone, or B-1 B-cell subsets and found that small numbers of each subset interacted with naïve antigen-specific T cells. Although antigen expressed by B-1 B cells induced the most T-cell division, divided T cells subsequently disappeared from secondary lymphoid tissues. Independent of which B-cell subset presented antigen, the remaining T cells were rendered hyporesponsive, and this effect was not associated with Foxp3 expression. Our data show that physiologically relevant proportions of B cells can mediate peripheral T-cell tolerance, and suggest that the mechanisms of tolerance induction might differ among follicular, marginal zone, and B-1 B-cell subsets.

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Peripheral Tolerance Via the Anterior Chamber of the Eye: Role of B Cells in MHC Class I and II Antigen Presentation

Cited by 52 publications

References 41 publications

Thein vitro-Inductionof Type II Collagen-Specific Immune Tolerance in BALB/C Mice

Thein vitro-Inductionof Type II Collagen-Specific Immune Tolerance in BALB/C Mice

Innate responses of B cells

Peripheral CD4⁺T‐cell tolerance is induced in vivo by rare antigen‐bearing B cells in follicular, marginal zone, and B‐1 subsets

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Peripheral Tolerance Via the Anterior Chamber of the Eye: Role of B Cells in MHC Class I and II Antigen Presentation

Cited by 52 publications

References 41 publications

Thein vitro-Inductionof Type II Collagen-Specific Immune Tolerance in BALB/C Mice

Thein vitro-Inductionof Type II Collagen-Specific Immune Tolerance in BALB/C Mice

Innate responses of B cells

Peripheral CD4+T‐cell tolerance is induced in vivo by rare antigen‐bearing B cells in follicular, marginal zone, and B‐1 subsets

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Peripheral CD4⁺T‐cell tolerance is induced in vivo by rare antigen‐bearing B cells in follicular, marginal zone, and B‐1 subsets