CD83 Expression in CD4+ T Cells Modulates Inflammation and Autoimmunity

Reinwald, Simone; Wiethe, Carsten; Westendorf, Astrid M.; Breloer, Minka; Probst‐Kepper, Michael; Fleischer, Bernhard; Steinkasserer, Alexander; Buer, Jan; Hansen, Wiebke

doi:10.4049/jimmunol.180.9.5890

Cited by 67 publications

(86 citation statements)

References 52 publications

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“…This was associated with impaired induction of CD83 and CD27, both representing known FOXP3-regulating receptors [13,23,24]. Strikingly, lentiviral downregulation of FOXP3 with specific siRNA in T reg cells resulted in similar phenotypic changes and affected induction of GARP, CD83, and CD27.…”

Section: Garp Controls Foxp3 Via a Positive Feedback Loopmentioning

confidence: 88%

Perspectives on Regulatory T Cell Therapies

Probst‐Kepper

Kröger

Garritsen

et al. 2009

Transfus Med Hemother

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Adoptive transfer in animal models clearly indicate an essential role of CD4+ CD25+ FOXP3+ regulatory T (Treg) cells in prevention and treatment of autoimmune and graft-versus-host disease. Thus, Treg cell therapies and development of drugs that specifically enhance Treg cell function and development represent promising tools to establish dominant tolerance. So far, lack of specific markers to differentiate human Treg cells from activated CD4+ CD25+ effector T cells, which also express FOXP3 at different levels, hampered such an approach. Recent identification of the orphan receptor glycoprotein-A repetitions predominant (GARP or LRRC32) as Treg cell-specific key molecule that dominantly controls FOXP3 via a positive feedback loop opens up new perspectives for molecular and cellular therapies. This brief review focuses on the role of GARP as a safeguard of a complex regulatory network of human Treg cells and its implications for regulatory T cell therapies in autoimmunity and graft-versus-host disease.

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Section: Garp Controls Foxp3 Via a Positive Feedback Loopmentioning

confidence: 88%

Perspectives on Regulatory T Cell Therapies

Probst‐Kepper

Kröger

Garritsen

et al. 2009

Transfus Med Hemother

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“…Because it is strongly up-regulated on murine and human dendritic cells (DC) 3 upon activation, CD83 used to be described as a highly specific maturation marker for DC (4,5). Many other studies, however, report CD83 surface expression on various cell types in vitro and in vivo, such as activated T and B lymphocytes (1, 6 -9), regulatory T cells (10), activated macrophages (11,12), and neutrophils (13,14), as well as a regulatory subset of NK cells (15). There is also evidence for CD83 expression in the brain (2, 3) and on thymic epithelial cells (TEC) (16), thus demonstrating that CD83 expression is not DC specific.…”

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confidence: 99%

Engagement of CD83 on B Cells Modulates B Cell Function In Vivo

Kretschmer

Lüthje

Schneider

et al. 2009

The Journal of Immunology

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The transmembrane glycoprotein CD83 is an important regulator of both thymic T cell maturation and peripheral T cell response. Recent studies suggested that CD83 is also involved in the regulation of B cell maturation, activation, and homeostasis. In this study, we show that in vivo overexpression of CD83 dose dependently interfered with the Ig response to thymus-dependent and thymus-independent model Ag immunization. CD83 deficiency, in contrast, which was restricted to B cells in mixed bone marrow chimeras, led to unchanged or even slightly increased Ig responses. Strikingly, the engagement of CD83 that is naturally upregulated on wild-type B cells by injection of anti-CD83 mAb in vivo induced a 100-fold increase in the IgG1 response to immunization. Kinetic analysis revealed that CD83 had to be engaged simultaneously or shortly after the B cell activation through injection of Ag, to modulate the IgG1 secretion. Furthermore, using mixed bone marrow chimeras in which either selectively the B cells or the dendritic cells were CD83 deficient, we demonstrate that anti-CD83 mAb mediated its biologic effect by engaging CD83 on B cells and not on CD11c ؉ dendritic cells. Taken together, we provide strong evidence that CD83 transduces regulatory signals into the very B cell on which it is expressed.

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“…Even though CD83 was mainly used as a selective marker for mature dendritic cells (DCs) (2,3), it is also expressed on a variety of other cell types, including thymus epithelial cells (4), T cells (5), and especially regulatory T cells (6,7) and B cells (8). Interestingly, it was shown that CD83 expression on thymus epithelial cells is essential for CD4 + T cell development (4).…”

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CD83 Modulates B Cell Activation and Germinal Center Responses

Krzyzak

Seitz

Urbat

et al. 2016

The Journal of Immunology

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CD83 is a maturation marker for dendritic cells. In the B cell lineage, CD83 is expressed especially on activated B cells and on light zone B cells during the germinal center (GC) reaction. The function of CD83 during GC responses is unclear. CD83−/− mice have a strong reduction of CD4+ T cells, which makes it difficult to analyze a functional role of CD83 on B cells during GC responses. Therefore, in the present study we generated a B cell–specific CD83 conditional knockout (CD83 B-cKO) model. CD83 B-cKO B cells show defective upregulation of MHC class II and CD86 expression and impaired proliferation after different stimuli. Analyses of GC responses after immunization with various Ags revealed a characteristic shift in dark zone and light zone B cell numbers, with an increase of B cells in the dark zone of CD83 B-cKO mice. This effect was not accompanied by alterations in the level of IgG immune responses or by major differences in affinity maturation. However, an enhanced IgE response was observed in CD83 B-cKO mice. Additionally, we observed a strong competitive disadvantage of CD83-cKO B cells in GC responses in mixed bone marrow chimeras. Furthermore, infection of mice with Borrelia burgdorferi revealed a defect in bacterial clearance of CD83 B-cKO mice with a shift toward a Th2 response, indicated by a strong increase in IgE titers. Taken together, our results show that CD83 is important for B cell activation and modulates GC composition and IgE Ab responses in vivo.

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CD83 Expression in CD4+ T Cells Modulates Inflammation and Autoimmunity

Cited by 67 publications

References 52 publications

Perspectives on Regulatory T Cell Therapies

Perspectives on Regulatory T Cell Therapies

Engagement of CD83 on B Cells Modulates B Cell Function In Vivo

CD83 Modulates B Cell Activation and Germinal Center Responses

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