Continuous expression of CD83 on activated human CD4+ T cells is correlated with their differentiation into induced regulatory T cells

Chen,Liwen; Guan,Shihe; Zhou,Qiang; Sheng,Shouqin; Zhong,Fei; Wang,Qin

doi:10.3892/mmr.2015.3796

Continuous expression of CD83 on activated human CD4+ T cells is correlated with their differentiation into induced regulatory T cells

Authors:
- Liwen Chen
- Shihe Guan
- Qiang Zhou
- Shouqin Sheng
- Fei Zhong
- Qin Wang
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Affiliations: Department of Laboratory Medicine, The Second Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China, Department of Medical Research Center, The Second Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China, Department of Medical Oncology, The First Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China
Published online on: May 18, 2015 https://doi.org/10.3892/mmr.2015.3796
Pages: 3309-3314
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

CD83 is a widely recognized surface marker for mature dendritic cells, which are essential for priming naïve CD4+ T cells into effector cells. However, CD83 is also expressed on activated CD4+ T cells, which remains an enigma in T‑cell mediated immunity. Therefore, the identification of the biological features and regulation of the expression of CD83 on activated CD4+ T cells is important in understanding the function of CD83 in the adaptive immune response. The present study revealed a time‑dependent manner of the expression of CD83 on anti‑CD3/CD28‑stimulated human CD4+ T cells, which is characterized by the maximum expression at day 2 and a significant decrease at day 3. The reduced expression is not a result of a reduced rate of cell proliferation. The activation of interleukin‑2 and secretion of interferon‑γ accumulated progressively from day 1 to 3. Of note, sustained expression of CD83 was observed when CD4+ T cells were induced by transforming growth factor-β to differentiate into CD4+CD25+ forkhead box P3+ regulatory T (iTreg) cells. Confocal immunofluorescence microscopy analysis demonstrated that CD83 was highly co‑localized with CD25 on activated CD4+ T cells. In conclusion, the findings of the present study suggested that the continuous expression of CD83 on activated human CD4+ T cells is correlated with their differentiation into iTreg cells.

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1	Zhou LJ, Schwarting R, Smith HM and Tedder TF: A novel cell-surface molecule expressed by human interdigitating reticulum cells, Langerhans cells and activated lymphocytes is a new member of the Ig superfamily. J Immunol. 149:735–742. 1992.PubMed/NCBI
2	Zhou LJ and Tedder TF: CD14⁺ blood monocytes can differentiate into functionally mature CD83⁺ dendritic cells. Proc Natl Acad Sci USA. 93:2588–2592. 1996. View Article : Google Scholar
3	Stein MF, Lang S, Winkler TH, et al: Multiple interferon regulatory factor and NF-κB sites cooperate in mediating cell-type- and maturation-specific activation of the human CD83 promoter in dendritic cells. Mol Cell Biol. 33:1331–1344. 2013. View Article : Google Scholar : PubMed/NCBI
4	Fujimoto Y, Tu L, Miller AS, Bock C, Fujimoto M, Doyle C, Steeber DA and Tedder TF: CD83 expression influences CD4⁺ T cell development in the thymus. Cell. 108:755–767. 2002. View Article : Google Scholar : PubMed/NCBI
5	Tze LE, Horikawa K, Domaschenz H, et al: CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation. J Exp Med. 208:149–165. 2011. View Article : Google Scholar : PubMed/NCBI
6	Prechtel AT, Turza NM, Theodoridis AA and Steinkasserer A: CD83 knockdown in monocyte-derived dendritic cells by small interfering RNA leads to a diminished T cell stimulation. J Immunol. 178:5454–5464. 2007. View Article : Google Scholar : PubMed/NCBI
7	Kretschmer B, Lüthje K, Ehrlich S, Osterloh A, Piedavent M, Fleischer B and Breloer M: CD83 on murine APC does not function as a costimulatory receptor for T cells. Immunol Lett. 120:87–95. 2008. View Article : Google Scholar : PubMed/NCBI
8	Pinho MP, Migliori IK, Flatow EA and Barbuto JA: Dendritic cell membrane CD83 enhances immune responses by boosting intracellular calcium release in T lymphocytes. J Leukoc Biol. 95:755–762. 2014. View Article : Google Scholar
9	Dudziak D, Nimmerjahn F, Bornkamm GW and Laux G: Alternative splicing generates putative soluble CD83 proteins that inhibit T cell proliferation. J Immunol. 174:6672–6676. 2005. View Article : Google Scholar : PubMed/NCBI
10	Bock F, Rössner S, Onderka J, et al: Topical application of soluble CD83 induces IDO-mediated immune modulation, increases Foxp3+ T cells and prolongs allogeneic corneal graft survival. J Immunol. 191:1965–1975. 2013. View Article : Google Scholar : PubMed/NCBI
11	Starke C, Steinkasserer A, Voll RE and Zinser E: Soluble human CD83 ameliorates lupus in NZB/W F1 mice. Immunobiology. 218:1411–1415. 2013. View Article : Google Scholar : PubMed/NCBI
12	Yuan Y, Wan L, Chen Y, et al: Production and characterization of human soluble CD83 fused with the fragment crystallizable region of human IgG1 in Pichia pastoris. Appl Microbiol Biotechnol. 97:9409–9417. 2013. View Article : Google Scholar : PubMed/NCBI
13	Eckhardt J, Kreiser S, Döbbeler M, et al: Soluble CD83 ameliorates experimental colitis in mice. Mucosal Immunol. 7:1006–1018. 2014.PubMed/NCBI
14	Guo Y, Li R, Song X, et al: The Expression and characterization of functionally active soluble CD83 by pichia Pastoris using high-density fermentation. PLoS One. 9:e892642014. View Article : Google Scholar : PubMed/NCBI
15	Chen L, Zhu Y, Zhang G, Gao C, Zhong W and Zhang X: CD83-stimulated monocytes suppress T-cell immune responses through production of prostaglandin E2. Proc Natl Acad Sci USA. 108:18778–18783. 2011. View Article : Google Scholar : PubMed/NCBI
16	Reinwald S, Wiethe C, Westendorf AM, Breloer M, Probst-Kepper M, Fleischer B, Steinkasserer A, Buer J and Hansen W: CD83 expression in CD4⁺ T cells modulates inflammation and autoimmunity. J Immunol. 180:5890–5897. 2008. View Article : Google Scholar : PubMed/NCBI
17	Su LL, Iwai H, Lin JT and Fathman CG: The transmembrane E3 ligase GRAIL ubiquitinates and degrades CD83 on CD4+ T cells. J Immunol. 183:438–444. 2009. View Article : Google Scholar : PubMed/NCBI
18	Kumar S, Naqvi RA, Ali R, Rani R, Khanna N and Rao DN: CD4⁺CD25⁺ T regs with acetylated FoxP3 are associated with immune suppression in human leprosy. Mol Immunol. 56:513–520. 2013. View Article : Google Scholar : PubMed/NCBI
19	Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G and Wahl SM: Conversion of peripheral CD4+CD25− naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med. 198:1875–1886. 2003. View Article : Google Scholar : PubMed/NCBI
20	Kretschmer B, Kühl S, Fleischer B and Breloer M: Activated T cells induce rapid CD83 expression on B cells by engagement of CD40. Immunol Lett. 136:221–227. 2011. View Article : Google Scholar : PubMed/NCBI
21	Lechmann M, Shuman N, Wakeham A and Mak TW: The CD83 reporter mouse elucidates the activity of the CD83 promoter in B, T and dendritic cell populations in vivo. Proc Natl Acad Sci USA. 105:11887–11892. 2008. View Article : Google Scholar
22	Yamane H and Paul WE: Early signaling events that underlie fate decisions of naive CD4(⁺) T cells toward distinct T-helper cell subsets. Immunol Rev. 252:12–23. 2013. View Article : Google Scholar : PubMed/NCBI
23	Yu A and Malek TR: Selective availability of IL-2 is a major determinant controlling the production of CD4⁺CD25⁺Foxp3⁺ T regulatory cells. J Immunol. 177:5115–5121. 2006. View Article : Google Scholar : PubMed/NCBI
24	Barron L, Dooms H, Hoyer KK, Kuswanto W, Hofmann J, O'Gorman WE and Abbas AK: Cutting edge: mechanisms of IL-2-dependent maintenance of functional regulatory T cells. J Immunol. 185:6426–6430. 2010. View Article : Google Scholar : PubMed/NCBI
25	Rao PE, Petrone AL and Ponath PD: Differentiation and expansion of T cells with regulatory function from human peripheral lymphocytes by stimulation in the presence of TGF-β. J Immunol. 174:1446–1455. 2005. View Article : Google Scholar : PubMed/NCBI