B7-1 and B7-2 differentially control peripheral homeostasis of CD4+CD25+Foxp3+ regulatory T cells

Zeng, Menghua; Guinet, Elisabeth; Nouri-Shirazi, Mahyar

doi:10.1016/j.trim.2008.09.009

Cited by 27 publications

(31 citation statements)

References 45 publications

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“…2A and SI Appendix, Fig. S1) (22). Interestingly, along with reduced expression of cell-intrinsic activation and proliferation markers by peripheral Tregs remaining among splenocytes in B7-deficient mice or after CTLA4-Ig B7 blockade, Helios and Neuropilin-1 expression were each also diminished among Foxp3 + splenocytes, but not Foxp3 + thymocytes, suggesting the selective retention of peripherally induced Tregs with B7 deprivation (Fig.…”

Section: Resultsmentioning

confidence: 91%

Commensal microbes drive intestinal inflammation by IL-17–producing CD4 ⁺ T cells through ICOSL and OX40L costimulation in the absence of B7-1 and B7-2

Luo¹,

Jiang²,

Chaturvedi³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The costimulatory B7-1 (CD80)/B7-2 (CD86) molecules, along with T-cell receptor stimulation, together facilitate T-cell activation. This explains why in vivo B7 costimulation neutralization efficiently silences a variety of human autoimmune disorders. Paradoxically, however, B7 blockade also potently moderates accumulation of immune-suppressive regulatory T cells (Tregs) essential for protection against multiorgan systemic autoimmunity. Here we show that B7 deprivation in mice overrides the necessity for Tregs in averting systemic autoimmunity and inflammation in extraintestinal tissues, whereas peripherally induced Tregs retained in the absence of B7 selectively mitigate intestinal inflammation caused by Th17 effector CD4 + T cells. The need for additional immune suppression in the intestine reflects commensal microbe-driven T-cell activation through the accessory costimulation molecules ICOSL and OX40L. Eradication of commensal enteric bacteria mitigates intestinal inflammation and IL-17 production triggered by Treg depletion in B7-deficient mice, whereas re-establishing intestinal colonization with Candida albicans primes expansion of Th17 cells with commensal specificity. Thus, neutralizing B7 costimulation uncovers an essential role for Tregs in selectively averting intestinal inflammation by Th17 CD4 + T cells with commensal microbe specificity.

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Section: Resultsmentioning

confidence: 91%

Commensal microbes drive intestinal inflammation by IL-17–producing CD4 ⁺ T cells through ICOSL and OX40L costimulation in the absence of B7-1 and B7-2

Luo¹,

Jiang²,

Chaturvedi³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…It was previously shown that Tregs cocultured with mDCs from CD80-/CD86-deficient mice showed reduced survival, and B7 expression on DCs was deemed necessary for Treg maintenance. 18 However, this same study showed that normal thymic development and peripheral distribution of conventional T cells were not affected in CD80-/CD86-deficient mice. In accordance with this, we were able to generate functional iTregs from CD80 2/2 CD86 2/2 DKO mice (Figure 1b and c), indicating that, unlike nTregs, the induction and function of iTregs is not dependant on these molecules.…”

Section: Trogocytosis Of Cd80 and Cd86 By Itregs P Gu Et Al 143mentioning

confidence: 84%

“…17 In order to avoid the potential influence of endogenously expressed CD80 and CD86, we chose to study iTreg trogocytosis of CD80 and CD86 using CD80 2/2 CD86 2/2 DKO mice. However, mice that lack CD80 and CD86 show a dramatic reduction in nTreg frequency in the thymus, 18 indicating that these molecules are important for nTreg development. Whether iTreg generation and function would be affected by the CD80/CD86 DKO was not known.…”

Section: Functional Cd4mentioning

confidence: 99%

“…The reason for this difference is not known. Although CD80 and CD86 share the same receptors, they have distinct binding affinities and kinetics 18 and have been shown to have differential functions. 32,33 Levels of both proteins were equally expressed on mDCs prior to coculture (data not shown), ruling out increased availability of CD86 for trogocytosis.…”

Section: Trogocytosis Of Cd80 and Cd86 By Itregs P Gu Et Al 144mentioning

confidence: 99%

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Trogocytosis of CD80 and CD86 by induced regulatory T cells

Gao

D'Souza

et al. 2012

Cell Mol Immunol

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Trogocytosis is a process which involves the transfer of membrane fragments and cell surface proteins between cells. Various types of T cells have been shown to be able to acquire membrane-bound proteins from antigen-presenting cells and their functions can be modulated following trogocytosis. However, it is not known whether induced regulatory T cells (iTregs) can undergo trogocytosis, and if so, what the functional consequences of this process might entail. In this study, we show that iTregs can be generated from CD80 2/2 CD86 2/2 double knockout (DKO) mice. Using flow cytometry and confocal fluorescence microscopy, we demonstrate that iTregs generated from DKO mice are able to acquire both CD80 and CD86 from mature dendritic cells (mDCs) and that the acquisition of CD86 occurs to a higher extent than that of CD80. Furthermore, we found that after co-incubation with iTregs, dendritic cells (DCs) downregulate their surface expression of CD80 and CD86. The trogocytosis of both CD80 and CD86 occurs in a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), CD28 and programmed death ligand-1 (PDL1)-independent manner. Importantly, we showed that iTregs that acquired CD86 from mDCs expressed higher activation markers and their ability to suppress naive CD4 1 T-cell proliferation was enhanced, compared to iTregs that did not acquire CD86. These data demonstrate, for the first time, that iTregs can acquire CD80 and CD86 from mDCs, and the acquisition of CD86 may enhance their suppressive function. These findings provide novel understanding of the interaction between iTregs and DCs, suggesting that trogocytosis may play a significant role in iTreg-mediated immune suppression.

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“…We also described that a similar reduction in the Treg population was taking place in the liver of CD80 2/2 86 2/2 mice, thereby exacerbating the development of nonalcoholic steatohepatitis under HFD conditions (52). However, CD80 2/2 86 2/2 mice have an inborn deficiency in the development of Tregs, which explains the unexpected aggravation of DIO in these mice (54). We therefore believed it of interest to investigate whether antibody-mediated blockage of CD80/86 in a DIO mouse that contains Tregs would improve IR and AT inflammation and hepatosteatosis because it has been shown that CD80/86-mediated activation of effector T cells results in their proliferation and induces the secretion of proinflammatory cytokines, including TNF-a and IL-6 (32,40).…”

Section: T-cell Antigen-presenting Cell Interactions In Obesitymentioning

confidence: 99%

Immune Cell Crosstalk in Obesity: A Key Role for Costimulation?

et al. 2014

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In the past two decades, numerous experimental and clinical studies have established the importance of inflammation and immunity in the development of obesity and its metabolic complications, including insulin resistance and type 2 diabetes mellitus. In this context, T cells orchestrate inflammatory processes in metabolic organs, such as the adipose tissue (AT) and liver, thereby mediating obesity-related metabolic deterioration. Costimulatory molecules, which are present on antigen-presenting cells and naïve T cells in the AT, are known to mediate the crosstalk between the adaptive and innate immune system and to direct T-cell responses in inflammation. In this Perspectives in Diabetes article, we highlight the newest insights in immune cell interactions in obesity and discuss the role of costimulatory dyads in its pathogenesis. Moreover, the potential of therapeutic strategies that target costimulatory molecules in the metabolic syndrome is explored.

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B7-1 and B7-2 differentially control peripheral homeostasis of CD4+CD25+Foxp3+ regulatory T cells

Cited by 27 publications

References 45 publications

Commensal microbes drive intestinal inflammation by IL-17–producing CD4 ⁺ T cells through ICOSL and OX40L costimulation in the absence of B7-1 and B7-2

Commensal microbes drive intestinal inflammation by IL-17–producing CD4 ⁺ T cells through ICOSL and OX40L costimulation in the absence of B7-1 and B7-2

Trogocytosis of CD80 and CD86 by induced regulatory T cells

Immune Cell Crosstalk in Obesity: A Key Role for Costimulation?

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B7-1 and B7-2 differentially control peripheral homeostasis of CD4+CD25+Foxp3+ regulatory T cells

Cited by 27 publications

References 45 publications

Commensal microbes drive intestinal inflammation by IL-17–producing CD4 + T cells through ICOSL and OX40L costimulation in the absence of B7-1 and B7-2

Commensal microbes drive intestinal inflammation by IL-17–producing CD4 + T cells through ICOSL and OX40L costimulation in the absence of B7-1 and B7-2

Trogocytosis of CD80 and CD86 by induced regulatory T cells

Immune Cell Crosstalk in Obesity: A Key Role for Costimulation?

Contact Info

Product

Resources

About

Commensal microbes drive intestinal inflammation by IL-17–producing CD4 ⁺ T cells through ICOSL and OX40L costimulation in the absence of B7-1 and B7-2

Commensal microbes drive intestinal inflammation by IL-17–producing CD4 ⁺ T cells through ICOSL and OX40L costimulation in the absence of B7-1 and B7-2