Continuous expression of CD83 on activated human CD4+ T cells is correlated with their differentiation into induced regulatory T cells

Chen, Liwen; Guan, Sheng; Zhou, Qiang; Sheng, Shouqin; Zhong, Fei; Wang, Qin

doi:10.3892/mmr.2015.3796

Cited by 10 publications

(10 citation statements)

References 25 publications

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“…These murine data are further supported by studies in the human system, which also showed a distinct CD83 expression profile comparing anti-CD3/CD28-stimulated human effector versus regulatory T cells (23,37). Upon TCR-stimulation in vitro, human CD4 + T cells upregulate CD83 expression transiently with a maximum expression at day 2 followed by a strong decline after day 3 (37). By contrast, expanded human CD25 hi CD45RA + Tregs already reached their CD83 mRNA expression maximum 3 h after stimulation (23).…”

Section: Treg Differentiation and Stabilitymentioning

confidence: 61%

“…By contrast, expanded human CD25 hi CD45RA + Tregs already reached their CD83 mRNA expression maximum 3 h after stimulation (23). Strikingly, TCRstimulation of human and murine CD4 + T cells together with transforming growth factor beta (TGFβ) not only resulted in the expected differentiation into CD4 + CD25 + Foxp3 + iTregs but also in a sustained and stable CD83 expression (37,38). In addition, immunofluorescence microscopy revealed CD83 to colocalize with CD25 on those cells (37).…”

Section: Treg Differentiation and Stabilitymentioning

confidence: 99%

“…Strikingly, TCRstimulation of human and murine CD4 + T cells together with transforming growth factor beta (TGFβ) not only resulted in the expected differentiation into CD4 + CD25 + Foxp3 + iTregs but also in a sustained and stable CD83 expression (37,38). In addition, immunofluorescence microscopy revealed CD83 to colocalize with CD25 on those cells (37). Strong expression of the high affinity IL-2-receptor alpha-chain CD25 is essential for Treg cell survival, due to their inability to produce IL-2 for survival and proliferation.…”

Section: Treg Differentiation and Stabilitymentioning

confidence: 99%

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The CD83 Molecule – An Important Immune Checkpoint

et al. 2020

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The CD83 molecule has been identified to be expressed on numerous activated immune cells, including B and T lymphocytes, monocytes, dendritic cells, microglia, and neutrophils. Both isoforms of CD83, the membrane-bound as well as its soluble form are topic of intensive research investigations. Several studies revealed that CD83 is not a typical co-stimulatory molecule, but rather plays a critical role in controlling and resolving immune responses. Moreover, CD83 is an essential factor during the differentiation of T and B lymphocytes, and the development and maintenance of tolerance. The identification of its interaction partners as well as signaling pathways have been an enigma for the last decades. Here, we report the latest data on the expression, structure, and the signaling partners of CD83. In addition, we review the regulatory functions of CD83, including its striking modulatory potential to maintain the balance between tolerance versus inflammation during homeostasis or pathologies. These immunomodulatory properties of CD83 emphasize its exceptional therapeutic potential, which has been documented in specific preclinical disease models.

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Section: Treg Differentiation and Stabilitymentioning

confidence: 61%

Section: Treg Differentiation and Stabilitymentioning

confidence: 99%

Section: Treg Differentiation and Stabilitymentioning

confidence: 99%

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The CD83 Molecule – An Important Immune Checkpoint

et al. 2020

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“…CD83 was first described for Langerhans cells and activated lymphocytes. It is a conserved member of the immunoglobulin superfamily and is also known as one of the most characteristic cell surface markers for fully mature DCs in peripheral circulation (31,50,51). Although CD83 plays essential roles in both the central and peripheral immune systems, the underlying mechanisms by which CD83 regulates immune responses remain enigmatic.…”

Section: Discussionmentioning

confidence: 99%

The Nucleocapsid Protein and Nonstructural Protein 10 of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Enhance CD83 Production via NF-κB and Sp1 Signaling Pathways

Chen

Zhang

Bai

et al. 2017

J Virol

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Porcine reproductive and respiratory syndrome, caused by porcine reproductive and respiratory syndrome virus (PRRSV), is a panzootic disease that is one of the most economically costly diseases to the swine industry. A key aspect of PRRSV virulence is that the virus suppresses the innate immune response and induces persistent infection, although the underlying mechanisms are not well understood. The dendritic cell (DC) marker CD83 belongs to the immunoglobulin superfamily and is associated with DC activation and immunosuppression of T cell proliferation when expressed as soluble CD83 (sCD83). In this study, we show that PRRSV infection strongly stimulates CD83 expression in porcine monocyte-derived DCs (MoDCs) and that the nucleocapsid (N) protein and nonstructural protein 10 (nsp10) of PRRSV enhance CD83 promoter activity via the NF-κB and Sp1 signaling pathways. R43A and K44A amino acid substitution mutants of the N protein suppress the N protein-mediated increase of CD83 promoter activity. Similarly, P192-5A and G214-3A mutants of nsp10 (with 5 and 3 alanine substitutions beginning at residues P192 and G214, respectively) abolish the nsp10-mediated induction of the CD83 promoter. Using reverse genetics, four mutant viruses (rR43A, rK44A, rP192-5A, and rG214-3A) and four revertants [rR43A(R), rK44A(R), rP192-5A(R), and rG214-3A(R)] were generated. Decreased induction of CD83 in MoDCs was observed after infection by mutants rR43A, rK44A, rP192-5A, and rG214-3A, in contrast to the results obtained using rR43A(R), rK44A(R), rP192-5A(R), and rG214-3A(R). These findings suggest that PRRSV N and nsp10 play important roles in modulating CD83 signaling and shed light on the mechanism by which PRRSV modulates host immunity. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically costly pathogens affecting the swine industry. It is unclear how PRRSV inhibits the host's immune response and induces persistent infection. The dendritic cell (DC) marker CD83 belongs to the immunoglobulin superfamily and has previously been associated with DC activation and immunosuppression of T cell proliferation and differentiation when expressed as soluble CD83 (sCD83). In this study, we found that PRRSV infection induces sCD83 expression in porcine MoDCs via the NF-κB and Sp1 signaling pathways. The viral nucleocapsid protein, nonstructural protein 1 (nsp1), and nsp10 were shown to enhance CD83 promoter activity. Amino acids R43 and K44 of the N protein, as well as residues 192 to 196 (P192-5) and 214 to 216 (G214-3) of nsp10, play important roles in CD83 promoter activation. These findings provide new insights into the molecular mechanism of immune suppression by PRRSV.

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“…In addition, it is induced on activated human B cells (12,13), monocytes (14), macrophages (14), neutrophils (15), and a regulatory subset of NK cells (16). We and others described CD83 on activated human T cells (6,10,17), but its expression on specific T cell subsets has not been well scrutinized (18).…”

mentioning

confidence: 99%

The Analysis of CD83 Expression on Human Immune Cells Identifies a Unique CD83+-Activated T Cell Population

Silveira

Hsu

et al. 2016

The Journal of Immunology

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CD83 is a member of the Ig gene superfamily, first identified in activated lymphocytes. Since then, CD83 has become an important marker for defining activated human dendritic cells (DC). Several potential CD83 mRNA isoforms have been described, including a soluble form detected in human serum, which may have an immunosuppressive function. To further understand the biology of CD83, we examined its expression in different human immune cell types before and after activation using a panel of mouse and human anti-human CD83 mAb. The mouse anti-human CD83 mAbs, HB15a and HB15e, and the human anti-human CD83 mAb, 3C12C, were selected to examine cytoplasmic and surface CD83 expression, based on their different binding characteristics. Glycosylation of CD83, the CD83 mRNA isoforms, and soluble CD83 released differed among blood DC, monocytes, and monocyte-derived DC, and other immune cell types. A small T cell population expressing surface CD83 was identified upon T cell stimulation and during allogeneic MLR. This subpopulation appeared specifically during viral Ag challenge. We did not observe human CD83 on unstimulated human natural regulatory T cells (Treg), in contrast to reports describing expression of CD83 on mouse Treg. CD83 expression was increased on CD4, CD8 T, and Treg cells in association with clinical acute graft-versus-host disease in allogeneic hematopoietic cell transplant recipients. The differential expression and function of CD83 on human immune cells reveal potential new roles for this molecule as a target of therapeutic manipulation in transplantation, inflammation, and autoimmune diseases.

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Continuous expression of CD83 on activated human CD4+ T cells is correlated with their differentiation into induced regulatory T cells

Cited by 10 publications

References 25 publications

The CD83 Molecule – An Important Immune Checkpoint

The CD83 Molecule – An Important Immune Checkpoint

The Nucleocapsid Protein and Nonstructural Protein 10 of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Enhance CD83 Production via NF-κB and Sp1 Signaling Pathways

The Analysis of CD83 Expression on Human Immune Cells Identifies a Unique CD83+-Activated T Cell Population

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