Murine CD83-positive T cells mediate suppressor functions in vitro and in vivo

Kreiser, Simon; Eckhardt, Jenny; Kuhnt, Christine; Stein, Marcello F.; Krzyzak, Lena; Seitz, Christine; Tucher, Christine; Knippertz, Ilka; Becker, Christoph; Günther, Claudia; Steinkasserer, Alexander; Lechmann, Matthias

doi:10.1016/j.imbio.2014.08.005

Cited by 30 publications

(38 citation statements)

References 57 publications

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“…In our experiment, we showed that CD83 is upregulated on CD4 + T cells during pregnancy and the proportion of CD4 + CD25 + T cells that are positive for CD83 increases throughout the stages of pregnancy. CD83 expression particularly on CD4 + CD25 + T cells is linked to immunosuppressive phenotype (39, 40). Additionally, our results are in agreement with the well-studied pregnancy-supporting role of regulatory T cells (70, 71).…”

Section: Discussionmentioning

confidence: 99%

“…While reports implicating silencing of CD83 expression on antigen-specific CD4 + T cells showed an impaired proliferative capacity and reduced cytokine secretion, this may not apply to all CD4 + T cell populations or it may represent a mechanism to avoid over-reactive CD4 + T cells (38–40). Indeed, CD83 overexpression in murine naïve CD4 + T cells induces regulatory T cell-specific FOXP3 expression and confers in vivo tolerogenic properties (39).…”

Section: Introductionmentioning

confidence: 94%

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A Kinetic Study of CD83 Reveals an Upregulation and Higher Production of sCD83 in Lymphocytes from Pregnant Mice

et al. 2017

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For the normal development of pregnancy, a balance between immune tolerance and defense is crucial. However, the mechanisms mediating such a balance are not fully understood. CD83 is a transmembrane protein whose expression has been linked to anti-inflammatory functions of T and B cells. The soluble form of CD83, released by cleavage of the membrane-bound protein, has strong anti-inflammatory properties and was successfully tested in different mouse models. It is assumed that this molecule contributes to the establishment of immune tolerance. Therefore, we postulated that the expression of CD83 is crucial for immune tolerance during pregnancy in mice. Here, we demonstrated that the membrane-bound form of CD83 was upregulated in T and B cells during allogeneic murine pregnancies. An upregulation was also evident in the main splenic B cell subtypes: marginal zone, follicular zone, and transitional B cells. We also showed that there was an augmentation in the number of CD83+ cells toward the end of pregnancy within splenic B and CD4+ T cells, while CD83+ dendritic cells were reduced in spleen and inguinal lymph nodes of pregnant mice. Additionally, B lymphocytes in late-pregnancy presented a markedly higher sensitivity to LPS in terms of CD83 expression and sCD83 release. Progesterone induced a dosis-dependent upregulation of CD83 on T cells. Our data suggest that the regulation of CD83 expression represents a novel pathway of fetal tolerance and protection against inflammatory threats during pregnancy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

A Kinetic Study of CD83 Reveals an Upregulation and Higher Production of sCD83 in Lymphocytes from Pregnant Mice

et al. 2017

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“…One well-characterized marker for this phenotypic transition from immature to mature DCs is the expression of the CD83 molecule (4,5). This member of the Ig superfamily is expressed primarily on activated leukocytes, including DCs and regulatory T cells (Tregs), as well as on thymic epithelial cells (TECs) (6)(7)(8)(9). A soluble form of CD83 (sCD83), comprising the extracellular domain, was detected at low levels in sera of healthy individuals and in increased concentrations in patients with hematological malignancies (10)(11)(12), and reports suggested B cells as a major source of naturally occurring sCD83 (13).…”

Section: Introductionmentioning

confidence: 99%

CD83 orchestrates immunity toward self and non-self in dendritic cells

Wild¹,

Krzyzak²,

Peckert³

et al. 2019

JCI Insight

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“…The transmembrane form of CD83 is expressed on mature dendritic cells (DCs), B cells, macrophages, activated T cells and T regulatory cells, and thymic epithelial cells (3,4). The expression on DCs is involved in the activation of T cell-mediated immune responses (5)(6)(7)(8); however, a soluble form of CD83, generated by splice variants or by shedding, inhibits T cell proliferation (9).…”

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confidence: 99%

Soluble CD83 Inhibits T Cell Activation by Binding to the TLR4/MD-2 Complex on CD14+ Monocytes

Horvatinovich

Grogan

Norris

et al. 2017

The Journal of Immunology

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The transmembrane protein CD83, expressed on APCs, B cells, and T cells, can be expressed as a soluble form generated by alternative splice variants and/or by shedding. Soluble CD83 (sCD83) was shown to be involved in negatively regulating the immune response. sCD83 inhibits T cell proliferation in vitro, supports allograft survival in vivo, prevents corneal transplant rejection, and attenuates the progression and severity of autoimmune diseases and experimental colitis. Although sCD83 binds to human PBMCs, the specific molecules that bind sCD83 have not been identified. In this article, we identify myeloid differentiation factor-2 (MD-2), the coreceptor within the TLR4/MD-2 receptor complex, as the high-affinity sCD83 binding partner. TLR4/MD-2 mediates proinflammatory signal delivery following recognition of bacterial LPSs. However, altering TLR4 signaling can attenuate the proinflammatory cascade, leading to LPS tolerance. Our data show that binding of sCD83 to MD-2 alters this signaling cascade by rapidly degrading IL-1R–associated kinase-1, leading to induction of the anti-inflammatory mediators IDO, IL-10, and PGE2 in a COX-2–dependent manner. sCD83 inhibited T cell proliferation, blocked IL-2 secretion, and rendered T cells unresponsive to further downstream differentiation signals mediated by IL-2. Therefore, we propose the tolerogenic mechanism of action of sCD83 to be dependent on initial interaction with APCs, altering early cytokine signal pathways and leading to T cell unresponsiveness.

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Murine CD83-positive T cells mediate suppressor functions in vitro and in vivo

Cited by 30 publications

References 57 publications

A Kinetic Study of CD83 Reveals an Upregulation and Higher Production of sCD83 in Lymphocytes from Pregnant Mice

A Kinetic Study of CD83 Reveals an Upregulation and Higher Production of sCD83 in Lymphocytes from Pregnant Mice

CD83 orchestrates immunity toward self and non-self in dendritic cells

Soluble CD83 Inhibits T Cell Activation by Binding to the TLR4/MD-2 Complex on CD14+ Monocytes

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