TY - JOUR
T1 - Annexin V expression on CD4+ T cells with regulatory function
AU - Bollinger, Anna Lena
AU - Bollinger, Thomas
AU - Rupp, Jan
AU - Shima, Kensuke
AU - Gross, Natalie
AU - Padayachy, Laura
AU - Chicheportiche, Rachel
AU - Puga Yung, Gisella L.
AU - Seebach, Jörg Dieter
N1 - Funding Information:
Author contributions: ALB and TB performed the experiments, designed the study and wrote the paper; RP designed the study for microarray comparisons; LP and RC performed the experiments of T‐cell expansions and characterization; NG and KS performed Western blot experiments; GPY performed experiments, data analysis and manuscript preparation; and JDS was involved in experimental design, wrote the paper and gave final approval. This work was funded by the DFG, BO‐3646/1‐1, BO‐3656/1‐1, SFB 654 TP C8, the University of Lübeck (SPP MIA/TP A2), Bollinger 50011 (Klinikum Bayreuth); SNSF grants 310030_159594 and 320030_138376; and a Private Foundation. We thank the Division of Immunology and Allergology of the University Hospitals of Geneva, Switzerland, and members for technical assistance and advice, D. Ehirchiou for technical help with the flow assay experiments, M. Freitas Monteiro and A. Real for PBMC isolation, the Transcriptome Laboratory of the University of Göttingen, G. Salinas‐Riester, C. Pommerenke and L. Opitz for their support with the microarray analysis, and the University of Lübeck, K. Wischnat and S. Gies for cell preparations used in microarray analysis.
Publisher Copyright:
© 2019 John Wiley & Sons Ltd
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Regulatory T (Treg) cells induce immunologic tolerance by suppressing effector functions of conventional lymphocytes in the periphery. On the other hand, immune silencing is mediated by recognition of phosphatidylserine (PS) on apoptotic cells by phagocytes. Here we describe expression of the PS-binding protein Annexin V (ANXA5) in CD4+ CD25hi Treg cells at the mRNA and protein levels. CD4+ ANXA5+ T cells constitute about 0·1%–0·6% of peripheral blood CD3+ T cells, exhibit co-expression of several Treg markers, such as Forkhead box P3, programmed cell death protein-1, cytotoxic T-lymphocyte antigen-4 and CD38. In vitro, ANXA5+ Treg cells showed enhanced adhesion to PS+ endothelial cells. Stimulated by anti-CD3 and PS+ syngeneic antigen-presenting cells CD4+ ANXA5+ T cells expanded in the absence of exogenous interleukin-2. CD4+ ANXA5+ T cells suppressed CD4+ ANXA5− T-cell proliferation and mammalian target of rapamycin phosphorylation, partially dependent on cell contact. CD4+ ANXA5+ T-cell-mediated suppression was allo-specific and accompanied by an increased production of anti-inflammatory mediators. In vivo, using a model of delayed type hypersensitivity, murine CD4+ ANXA5+ T cells inhibited T helper type 1 responses. In conclusion, we report for the first time expression of ANXA5 on a subset of Treg cells that might bridge classical regulatory Treg function with immune silencing.
AB - Regulatory T (Treg) cells induce immunologic tolerance by suppressing effector functions of conventional lymphocytes in the periphery. On the other hand, immune silencing is mediated by recognition of phosphatidylserine (PS) on apoptotic cells by phagocytes. Here we describe expression of the PS-binding protein Annexin V (ANXA5) in CD4+ CD25hi Treg cells at the mRNA and protein levels. CD4+ ANXA5+ T cells constitute about 0·1%–0·6% of peripheral blood CD3+ T cells, exhibit co-expression of several Treg markers, such as Forkhead box P3, programmed cell death protein-1, cytotoxic T-lymphocyte antigen-4 and CD38. In vitro, ANXA5+ Treg cells showed enhanced adhesion to PS+ endothelial cells. Stimulated by anti-CD3 and PS+ syngeneic antigen-presenting cells CD4+ ANXA5+ T cells expanded in the absence of exogenous interleukin-2. CD4+ ANXA5+ T cells suppressed CD4+ ANXA5− T-cell proliferation and mammalian target of rapamycin phosphorylation, partially dependent on cell contact. CD4+ ANXA5+ T-cell-mediated suppression was allo-specific and accompanied by an increased production of anti-inflammatory mediators. In vivo, using a model of delayed type hypersensitivity, murine CD4+ ANXA5+ T cells inhibited T helper type 1 responses. In conclusion, we report for the first time expression of ANXA5 on a subset of Treg cells that might bridge classical regulatory Treg function with immune silencing.
UR - http://www.scopus.com/inward/record.url?scp=85075242469&partnerID=8YFLogxK
U2 - 10.1111/imm.13140
DO - 10.1111/imm.13140
M3 - Journal articles
C2 - 31642515
AN - SCOPUS:85075242469
SN - 0019-2805
VL - 159
SP - 205
EP - 220
JO - Immunology
JF - Immunology
IS - 2
ER -