Type II Collagen Induces Peripheral Tolerance in BALB/c Mice via the Generation of CD8+ T Regulatory Cells

Farooq, Shukkur M.; Ashour, Hossam M.

doi:10.1371/journal.pone.0048635

Cited by 38 publications

(47 citation statements)

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“…We performed DTH assays in a similar manner to that which had been carried out previously (9). Briefly, 200 ug of CII in 20 ul was injected intradennally into the left ear pinna, and 20 ul 10 mM acetic acid was injected into the right ear pinna (internal control).…”

Section: Dth Assaymentioning

confidence: 99%

“…Generation of splenic Tregs in vivo was carried out as before (9). Briefly, mice were subcutaneously immunized with 250 ug CII in CFA (1:1) seven days after the ACAID Cll-specific APCs injection via the intravenous route.…”

Section: In Vivo 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%

“…The clinical significance of CII in rheumatoid arthritis is established (8). We have recently shown that CII induced peripheral tolerance when injected into the AC of the eye of Balblc mice (9). Due to the reported functional similarities of in vitro-generated ocular-like ACAID APCs and eye-derived APCs (10, 11), we hypothesized that in vitro-generated ACAID macrophages that are specific to CII could induce CII-specific immune tolerance, similar to what we reported previously with the AC injection of CII (9).…”

mentioning

confidence: 99%

“…We have recently shown that CII induced peripheral tolerance when injected into the AC of the eye of Balblc mice (9). Due to the reported functional similarities of in vitro-generated ocular-like ACAID APCs and eye-derived APCs (10, 11), we hypothesized that in vitro-generated ACAID macrophages that are specific to CII could induce CII-specific immune tolerance, similar to what we reported previously with the AC injection of CII (9). Following the intravenous injection of CIIspecific ACAID APCs and Cll-specific Tregs into Balblc mice, we tested for ACAID generation and examined the regulatory functions of whole spleen cells, T cells, CD4+ CD25+ T cells, and CD8+ T cells.…”

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: Dth Assaymentioning

confidence: 99%

Section: In Vivo 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%

mentioning

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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Adaptive Immunity in Schizophrenia: Functional Implications of T Cells in the Etiology, Course and Treatment

Debnath

2015

J Neuroimmune Pharmacol

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Schizophrenia is a severe and highly complex neurodevelopmental disorder with an unknown etiopathology. Recently, immunopathogenesis has emerged as one of the most compelling etiological models of schizophrenia. Over the past few years considerable research has been devoted to the role of innate immune responses in schizophrenia. The findings of such studies have helped to conceptualize schizophrenia as a chronic low-grade inflammatory disorder. Although the contribution of adaptive immune responses has also been emphasized, however, the precise role of T cells in the underlying neurobiological pathways of schizophrenia is yet to be ascertained comprehensively. T cells have the ability to infiltrate brain and mediate neuro-immune cross-talk. Conversely, the central nervous system and the neurotransmitters are capable of regulating the immune system. Neurotransmitter like dopamine, implicated widely in schizophrenia risk and progression can modulate the proliferation, trafficking and functions of T cells. Within brain, T cells activate microglia, induce production of pro-inflammatory cytokines as well as reactive oxygen species and subsequently lead to neuroinflammation. Importantly, such processes contribute to neuronal injury/death and are gradually being implicated as mediators of neuroprogressive changes in schizophrenia. Antipsychotic drugs, commonly used to treat schizophrenia are also known to affect adaptive immune system; interfere with the differentiation and functions of T cells. This understanding suggests a pivotal role of T cells in the etiology, course and treatment of schizophrenia and forms the basis of this review.

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In vitro-induced cell-mediated immune deviation to encephalitogenic antigens

Farooq

2014

Brain, Behavior, and Immunity

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Type II Collagen Induces Peripheral Tolerance in BALB/c Mice via the Generation of CD8+ T Regulatory Cells

Cited by 38 publications

References 38 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

Adaptive Immunity in Schizophrenia: Functional Implications of T Cells in the Etiology, Course and Treatment

In vitro-induced cell-mediated immune deviation to encephalitogenic antigens

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