A Novel Mutation in CD83 Results in the Development of a Unique Population of CD4+ T Cells

Garcı́a-Martı́nez, León F.; Appleby, Mark W.; Staehling‐Hampton, Karen; Andrews, Dawn M.; Chen, Yuching; McEuen, Mark; Tang, Phuong; Rhinehart, Rebecca L.; Proll, Sean; Paeper, Bryan; Brunkow, Mary E.; Grandea, Andres G.; Howard, Edward D.; Walker, D.; Charmley, Patrick; Jonas, Mechthild; Shaw, Stevan; Latham, John; Ramsdell, Fred

doi:10.4049/jimmunol.173.5.2995

Cited by 46 publications

(81 citation statements)

References 21 publications

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“…1B), suggesting that CD83 does not participate in the function of CD8 ϩ T cells. Similar observations as published for CD83 Ϫ/Ϫ mice were described for CD83 mutant mice (17). The engineered genetic disruption of CD83 also impaired the development of CD4 ϩ T cells, while the CD8 ϩ single-positive thymocyte development and numbers were normal (17).…”

Section: Discussionsupporting

confidence: 83%

“…Similar observations as published for CD83 Ϫ/Ϫ mice were described for CD83 mutant mice (17). The engineered genetic disruption of CD83 also impaired the development of CD4 ϩ T cells, while the CD8 ϩ single-positive thymocyte development and numbers were normal (17). This defect in CD4 ϩ T cell development results from modifications of the thymic environment as CD83 Ϫ/Ϫ thymocytes and stem cells developed normally within WT mice (16), suggesting that CD83 expression on thymic epithelial cells contributes to CD4 ϩ but not CD8 ϩ T cell development within the thymus.…”

Section: Discussionsupporting

confidence: 72%

“…Its expression has been described in the brain and spleen (12) as well as in activated bone marrow-derived DCs (13) and activated B cells (14,15). Recent studies of mice deficient for CD83 have revealed that CD83 plays a central role in the thymic selection of double-positive thymocytes to single CD4-positive T cells, as these mice show a selective 75-90% reduction in peripheral CD4 ϩ T cells (16,17). Thus, CD83 expression on thymic epithelial cells seems to represent an additional regulatory component for CD4 ϩ T cell development in the thymus.…”

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confidence: 99%

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CD83 Expression in CD4+ T Cells Modulates Inflammation and Autoimmunity

Reinwald

Wiethe²,

Westendorf

et al. 2008

The Journal of Immunology

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The transmembrane protein CD83 has been initially described as a maturation marker for dendritic cells. Moreover, there is increasing evidence that CD83 also regulates B cell function, thymic T cell maturation, and peripheral T cell activation. Herein, we show that CD83 expression confers immunosuppressive function to CD4+ T cells. CD83 mRNA is differentially expressed in naturally occurring CD4+CD25+ regulatory T cells, and upon activation these cells rapidly express large amounts of surface CD83. Transduction of naive CD4+CD25− T cells with CD83 encoding retroviruses induces a regulatory phenotype in vitro, which is accompanied by the induction of Foxp3. Functional analysis of CD83-transduced T cells in vivo demonstrates that these CD83+Foxp3+ T cells are able to interfere with the effector phase of severe contact hypersensitivity reaction of the skin. Moreover, adoptive transfer of these cells prevents the paralysis associated with experimental autoimmune encephalomyelitis, suppresses proinflammatory cytokines IFN-γ and IL-17, and increases antiinflammatory IL-10 in recipient mice. Taken together, our data provide the first evidence that CD83 expression can contribute to the immunosuppressive function of CD4+ T cells in vivo.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 72%

mentioning

confidence: 99%

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CD83 Expression in CD4+ T Cells Modulates Inflammation and Autoimmunity

Reinwald

Wiethe²,

Westendorf

et al. 2008

The Journal of Immunology

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“…CD8 ϩ T cells in lupusprone mice are impaired in expansion, acquisition of memory, secretion of cytokine, and suppression of autoimmunity (8,82) and because CD83 appears to have a role in CD8 ϩ function, it is possible that down-regulation of the former could contribute to abnormal CD8 ϩ function in SLE. In addition, CD4 ϩ T cells that develop in a CD83 mutant animal fail to respond normally following allogeneic stimulation (83), at least in part due to an altered cytokine expression pattern characterized by an increased production of IL-4 and IL-10 and diminished IL-2 production, findings typically seen in SLE. Thus, absence or decrease of CD83 in SLE DCs may result in the generation of T cells with an altered activation and cytokine profile.…”

Section: Discussionmentioning

confidence: 99%

Aberrant Phenotype and Function of Myeloid Dendritic Cells in Systemic Lupus Erythematosus

Ding

Mehta

McCune

et al. 2006

The Journal of Immunology

133

106

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Systemic lupus erythematosus (SLE) is characterized by a systemic autoimmune response with profound and diverse T cell changes. Dendritic cells (DCs) are important orchestrators of immune responses and have an important role in the regulation of T cell function. The objective of this study was to determine whether myeloid DCs from individuals with SLE display abnormalities in phenotype and promote abnormal T cell function. Monocyte-derived DCs and freshly isolated peripheral blood myeloid DCs from lupus patients displayed an abnormal phenotype characterized by accelerated differentiation, maturation, and secretion of proinflammatory cytokines. These abnormalities were characterized by higher expression of the DC differentiation marker CD1a, the maturation markers CD86, CD80, and HLA-DR, and the proinflammatory cytokine IL-8. In addition, SLE patients displayed selective down-regulation of the maturation marker CD83 and had abnormal responses to maturation stimuli. These abnormalities have functional relevance, as SLE DCs were able to significantly increase proliferation and activation of allogeneic T cells when compared with control DCs. We conclude that myeloid DCs from SLE patients display significant changes in phenotype which promote aberrant T cell function and could contribute to the pathogenesis of SLE and organ damage.

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“…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).…”

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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A Novel Mutation in CD83 Results in the Development of a Unique Population of CD4+ T Cells

Cited by 46 publications

References 21 publications

CD83 Expression in CD4+ T Cells Modulates Inflammation and Autoimmunity

CD83 Expression in CD4+ T Cells Modulates Inflammation and Autoimmunity

Aberrant Phenotype and Function of Myeloid Dendritic Cells in Systemic Lupus Erythematosus

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

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