Antigen presentation by mouse CD4+ T cells involving acquired MHC class II:peptide complexes: another mechanism to limit clonal expansion?

Tsang, Julia Y. S.; Chai, Jian Guo; Lechler, Robert I.

doi:10.1182/blood-2002-04-1230

Cited by 104 publications

(127 citation statements)

References 30 publications

(35 reference statements)

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“…Prazma et al further described a loss of viability of CD83-deficient CD4 ϩ T cells. Regulation of MHCII expression is thought to limit T cell clonal expansion and thus control T cell responses (37). However, whether CD83 truly regulates MHCII expression and thus T cell responses requires additional investigation.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…CD4 + T cells that have captured agonist pMHC II complexes can subsequently present them to adjacent CD4 + T cells, and these T cells can proliferate in response to T cell-mediated presentation (83), but as the number of activated cells increases, this T-T cell interaction can result in apoptosis or the induction of anergy or tolerance or regulatory T cells (90)(91)(92). These mechanisms may serve to limit the clonol expansion (90).…”

Section: Suppressive Effect On Immune Responsesmentioning

confidence: 99%

“…These mechanisms may serve to limit the clonol expansion (90). The adoptive antigen-specific CD4 + regulatory T cells including Tr1 and Th3 play an important role in immune suppression of autoimmune diseases and antitumor immunity (93).…”

Section: Suppressive Effect On Immune Responsesmentioning

confidence: 99%

Intercellular Trogocytosis Plays an Important Role in Modulation of Immune Responses

et al. 2008

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“…A previous experiment demonstrated that irradiation at this dose had no significant effect on L-kynurenine production by MCEC following IDO cDNA transfection (data not shown). Proliferation was measured by a 16-h pulse with [ 3 H]thymidine (10 lL, *5 lCi/mL, Amersham Pharmacia Biotech) [46].…”

Section: T Cell Proliferation Assaysmentioning

confidence: 99%

Function of indoleamine 2,3‐dioxygenase in corneal allograft rejection and prolongation of allograft survival by over‐expression

et al. 2006

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Indoleamine 2,3-dioxygenase (IDO) suppresses T cell responses by its action in catabolising tryptophan. It is important in maintenance of immune privilege in the placenta. We investigated the activity of IDO in the cornea, following corneal transplantation and the effect of IDO over-expression in donor corneal endothelium on the survival of corneal allografts. IDO expression was analysed and functional activity was quantified in normal murine cornea and in corneas following transplantation as allografts. Low levels of IDO, at both mRNA and protein levels, was detected in the normal cornea, up-regulated by IFN-c and TNF. Expression of IDO in cornea was significantly increased following corneal transplantation. However, inhibition of IDO activity in vivo had no effect on graft survival. Following IDO cDNA transfer, murine corneal endothelial cells expressed functional IDO, which was effective at inhibiting allogeneic T cell proliferation. Over-expression of IDO in donor corneal allografts resulted in prolonged graft survival. While, on one hand, our data indicate that IDO may augment corneal immune privilege, up-regulated IDO activity following cytokine stimulation may serve to inhibit inflammatory cellular responses. While increasing IDO mRNA expression was found in allogeneic corneas at rejection, over-expression in donor cornea was found to significantly extend survival of allografts.

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Antigen presentation by mouse CD4+ T cells involving acquired MHC class II:peptide complexes: another mechanism to limit clonal expansion?

Cited by 104 publications

References 30 publications

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

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

Intercellular Trogocytosis Plays an Important Role in Modulation of Immune Responses

Function of indoleamine 2,3‐dioxygenase in corneal allograft rejection and prolongation of allograft survival by over‐expression

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