Annexin V expression on CD4<sup>+</sup> T cells with regulatory function

Article Article scientifique Article Annexin V expression on CD4<sup>+</sup> T cells with regulatory function eng 2020 author Bollinger Annalena 749864 author Bollinger Thomas 747746 author Rupp Jan author Shima Kensuke author Gross Natalie author Padayachy Laura 660292 author Chicheportiche Rachel 25901 author Puga Yung Gisella 0000-0002-2283-7798 666337 author Seebach Jorg Dieter 647894 205-220 10.1111/imm.13140 31642515 0019-2805 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. Animals Annexin A5/genetics/immunology/metabolism Cell adhesion Cell proliferation Cultured cells Cytokines/immunology/metabolism Disease models animal Endothelial cells/immunology/metabolism Humans Hypersensitivity delayed/genetics/immunology/metabolism Lymphocyte activation Male Mice inbred C57BL Phenotype Phosphatidylserines/metabolism Phosphorylation Signal transduction T-lymphocytes regulatory/immunology/metabolism TOR serine-threonine kinases/metabolism Th1 cells/immunology/metabolism Dewey 570 Dewey 616 Swiss National Science Foundation Strategies to promote tolerance and reduce rejection in rat-to-mouse xenotransplantation models 159594 CH Project funding Swiss National Science Foundation Transgenic strategies to overcome cellular rejection in pig-to-human xenotransplantation 138376 CH Project funding 43 Département de biologie moléculaire 161 56 Département de médecine 221 false 518 Cellules NK et récepteurs FcyR dans l'auto-immunité et le rejet de xénotransplantation 856 Immunology 159 2 70b64bda-0eb1-4dd9-9417-b2c91d5274a9 Article (Published version) Restricted imm.13140.pdf 1751972 application/pdf 3b1af74c-f2a1-43d2-b0e6-cf22b23f84ca Supplemental data Restricted imm13140-sup-0001-figs1.docx 455719 application/vnd.openxmlformats-officedocument.wordprocessingml.document restrictedAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire Faculté de médecine / Section de médecine clinique / Département de médecine

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Annexin V expression on CD4⁺ T cells with regulatory function	Immunology			2020	408	3

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Bollinger, Annalena