CD83 expression on dendritic cells and T cells: Correlation with effective immune responses

Aerts-Toegaert, Cindy; Heirman, Carlo; Tuyaerts, Sandra; Corthals, Jurgen; Aerts, Joeri L.; Bonehill, Aude; Thielemans, Kris; Breckpot, Karine

doi:10.1002/eji.200636535

Cited by 176 publications

(125 citation statements)

References 33 publications

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“…Specifically, allogenic T cell stimulation by human DCs is reduced when cell surface CD83 expression is down-regulation by RNA interference [19,47]. By contrast, the transient overexpression of CD83 by immature and mature human DCs enhances their T cell stimulatory capacity [19]. These results parallel studies where CD83 overexpression by a human B cell line and a mouse melanoma cell line enhances T cell proliferation and INF-γ production in vitro and in vivo [6,9].…”

Section: Membrane Cd83 Functionmentioning

confidence: 68%

“…CD83 expression is detectable on human lymphocytes activated in vitro and is present at low levels on many human B and T cell lines [1,[17][18][19]. More specifically, CD83 is not detectable at significant levels on circulating human lymphocytes or NK cells, but CD83 is detectable on blasting lymphocytes following mitogen stimulation.…”

Section: Cd83 Expressionmentioning

confidence: 99%

Section: Membrane Cd83 Functionmentioning

confidence: 99%

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Dendritic cell CD83: A therapeutic target or innocent bystander?

Prazma

Tedder

2008

Immunology Letters

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CD83 represents an intriguing target for immunotherapy due to its preferential expression on mature DCs, the most efficient of antigen presenting cells. Based on its restricted expression pattern, structure, and the paucity of CD4 + T cells in CD83-deficient mice, multiple immunologically important functions for CD83 during immune responses have been proposed. Indeed, several studies have reported that CD83 blockade using soluble receptor constructs inhibits T cell responses in vitro and in vivo, can affect autoimmune disease development and progression, and can inhibit transplant rejection. However, others have not been able to reproduce some of these findings, and antigen presenting cells deficient in CD83 expression or expressing a mutated form of CD83 induce normal T cell responses in vitro. This review examines the controversy surrounding CD83 function, alleged CD83 ligands, the potential therapeutic utility of recombinant proteins targeting CD83 function, and the importance of soluble serum CD83. While the validity of multiple previous studies needs to be confirmed, CD83 remains a fascinating cell surface molecule with a unique pattern of expression that has multiple confirmed functions in regulating immune system development and function.

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Section: Membrane Cd83 Functionmentioning

confidence: 68%

Section: Cd83 Expressionmentioning

confidence: 99%

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Dendritic cell CD83: A therapeutic target or innocent bystander?

Prazma

Tedder

2008

Immunology Letters

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“…Lipofection of siRNA into DCs. The delivery of siRNA by lipofection was performed as described previously (42). In brief, 12.5 l of 20 M annealed siRNA was incubated with 5 l of Lipofectamine 2000 (Invitrogen) in a volume of 500 l of serum free Optimem (Invitrogen) at room temperature for 20 min.…”

Section: Transfection Of DC With Sirnamentioning

confidence: 99%

Attenuated Expression of A20 Markedly Increases the Efficacy of Double-Stranded RNA-Activated Dendritic Cells As an Anti-Cancer Vaccine

Breckpot

Aerts-Toegaert

Heirman

et al. 2009

The Journal of Immunology

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A20 is a zinc finger protein with ubiquitin-modifying activity. A20 has been described as negatively regulating signaling induced by the TNF receptor and TLR family in a number of cell types, including mouse bone marrow-derived dendritic cells (DCs). However, the expression and effect of A20 in activated human monocyte-derived DCs have not been previously evaluated. We report that DCs activated with the TLR3 ligand poly(I:C) up-regulate A20. Down-regulating A20 demonstrated its role in the functional activation of DCs. A20 down-regulated DCs showed higher activation of the transcription factors NF-κB and activator protein-1, which resulted in increased and sustained production of IL-6, IL-10, and IL-12p70. We additionally silenced the immunosuppressive cytokine IL-10 and demonstrated that IL-10 inhibits T cell proliferation. We further demonstrated that A20 down-regulated DCs skew naive CD4+ T cells toward IFN-γ producing Th1 cells, a process which is dependent on IL-12p70 and which is unaffected by IL-10. Furthermore, A20 and/or IL-10 down-regulated DCs had an enhanced capacity to prime Melan-A/MART-1 specific CD8+ T cells. Finally, we demonstrated that potent T cell stimulatory DCs are generated by the simultaneous delivery of poly(I:C12U), A20, or A20/IL-10 small interfering RNA and Ag-encoding mRNA, introducing a one step approach to improve DC-based vaccines. Together these findings demonstrate that A20 negatively regulates NF-κB and activator protein-1 in DCs and that down-regulation of A20 results in DCs with enhanced T cell stimulatory capacity.

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“…In addition, CD83 may regulate the intercellular interactions between DCs and peripheral T and B cells (12,(23)(24)(25). In vitro culture of either human or murine lymphocytes in the presence of sCD83 inhibits their proliferation (26,27).…”

mentioning

confidence: 99%

The CD83 reporter mouse elucidates the activity of the CD83 promoter in B, T, and dendritic cell populationsin vivo

Lechmann

Shuman

Wakeham

et al. 2008

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

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CD83 is the major surface marker identifying mature dendritic cells (DCs). In this study, we report the generation of reporter mice expressing EGFP under the control of the CD83 promoter. We have used these mice to characterize CD83 expression by various immune system cell types both in vivo and ex vivo and under steady-state conditions and in response to stimulation with a Toll-like receptor (TLR) ligand. With those mice we could prove in vivo that the CD83 promoter is highly active in all DCs and B cells in lymphoid organs. Interestingly, this promoter activity in B cells mainly depended on the stage of development, is up-regulated in the late pre-B cell stage, and was maintained on a high level in all peripheral B cells. We also confirmed that CD83 in those cells is mainly intracellular but is up-regulated after TLR stimulation. Otherwise, CD83 promoter activity in T cells seemed to depend on stimulation and could be found mainly in CD4 ؉ CD25 ؉ and CD8 ؉ CD25 ؉ T cells and in CD4 ؉ and CD8 ؉ memory cells. In addition, we identified the murine homologues of the human CD83 splice variants. In contrast to those in human, those extremely rare short transcripts were never found without the expression of the highly dominant full-length form. So, the murine CD83 surface expression is mainly regulated posttranslationally in vivo. Our CD83 reporter mice represent a useful mouse model for monitoring the activation status and migration of DCs and lymphocytes under various conditions, and our results provide much needed clarification of the true nature of CD83 promoter activity.immune system ͉ mouse model ͉ intravital microscopy T he primary cells mediating adaptive responses are T and B lymphocytes and dendritic cells (DCs). A DC's ontogeny, state of differentiation, and degree of maturation governs its expression of a plethora of membrane-bound and soluble molecules that can induce immunostimulatory and immunosuppressive responses (1-3). Maturing DCs up-regulate certain cell surface molecules that greatly enhance their ability to present antigen and activate naive CD4 ϩ and CD8 ϩ T cells. Among these molecules is CD83, first described by Zhou et al. (4), CD83 is one of the most useful markers for identifying mature DCs capable of activating naïve T cells (5-8). CD83 expression also occurs on certain T cell subsets (9, 10), B cells (10-12), and murine thymic epithelial cells (13,14). Studies of CD83 transcription have shown that it is mediated by NF-B during the induction of adaptive responses (15,16).CD83 is conserved from fish species to mammals (17), with mouse CD83 sharing 63% amino acid identity with human CD83 (18,19). To date, two protein isoforms of CD83 have been reported in humans: a membrane-bound form (mCD83) (5) and a soluble form (sCD83) (20). mCD83 is a highly glycosylated surface protein of the Ig superfamily with a molecular mass of 40-45 kDa (5, 21). mCD83 contains an extracellular Ig-like V domain at the N terminus, a short intracellular cytoplasmic domain of 39 aa, and one transmembrane domain (5). ...

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CD83 expression on dendritic cells and T cells: Correlation with effective immune responses

Cited by 176 publications

References 33 publications

Dendritic cell CD83: A therapeutic target or innocent bystander?

Dendritic cell CD83: A therapeutic target or innocent bystander?

Attenuated Expression of A20 Markedly Increases the Efficacy of Double-Stranded RNA-Activated Dendritic Cells As an Anti-Cancer Vaccine

The CD83 reporter mouse elucidates the activity of the CD83 promoter in B, T, and dendritic cell populationsin vivo

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