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Selected Publication:

Publication type: Journal Article
Document type: Full Paper

Year: 2015

Author(s): Käser, T; Mair, KH; Hammer, SE; Gerner, W; Saalmüller, A

Title: Natural and inducible Tregs in swine: Helios expression and functional properties.

Source: Dev Comp Immunol. 2015; 49(2):323-331



Authors Vetmeduni Vienna:

Gerner Wilhelm
Hammer Sabina
Käser Tobias
Mair Kerstin
Saalmüller Armin

Vetmed Research Units
Institute of Immunology


Abstract:
Within the population of regulatory T cells (Tregs) natural Tregs (nTregs) and inducible Tregs (iTregs) can be distinguished. Although information about Tregs in swine exists, porcine iTregs were not under investigation yet. In this study, Foxp3(+) iTregs were generated from CD4(+)Foxp3(-) T cells by in vitro stimulation in the presence of IL-2 and TGF-β. In comparison to ex vivo Tregs these iTregs had a similar suppressive capacity on the proliferation of CD3-stimulated PBMC, caused higher levels of IL-10 in PBMC/Treg co-cultures, but did not suppress IFN-γ levels. The Ikaros family member Helios is currently discussed to distinguish iTregs and nTregs or to serve as an activation marker of Tregs. In this study, we demonstrate the cross-reactivity of an anti-mouse/human Helios mAb with porcine Helios. Flow cytometric analyses with this antibody showed that porcine iTregs do not express Helios after in vitro iTreg induction. Nevertheless, thymic Foxp3(+) T cells, which arise at the CD4/CD8α single-positive stage of T-cell development and are defined as nTregs, entirely expressed Helios. Although this might suggest the suitability of Helios as an nTreg-iTreg differentiation marker we also found that Helios(-) Tregs displayed a phenotype of naive CD4(+) T cells in vivo. Since iTregs are by definition activated/differentiated Tregs, this finding precludes that all Helios(-) Tregs are iTregs and thus also the use of Helios as a selection marker for porcine nTregs. Furthermore, Helios(+) Tregs displayed a more differentiated phenotype indicating that Helios might rather serve as a Treg activation/differentiation marker.

Keywords Pubmed: Amino Acid Sequence
Animals
Antigens, CD3/biosynthesis
Biomarkers
Cell Differentiation/immunology
Cell Line
Cell Proliferation
Cells, Cultured
Coculture Techniques
Forkhead Transcription Factors/metabolism
HEK293 Cells
Humans
Ikaros Transcription Factor/immunology*
Interferon-gamma/biosynthesis*
Interleukin-10/metabolism
Interleukin-2/immunology
Leukocytes, Mononuclear/immunology*
Lymphocyte Activation/immunology
Molecular Sequence Data
Swine
T-Lymphocytes, Regulatory/cytology
T-Lymphocytes, Regulatory/immunology*
Transforming Growth Factor beta/immunology
Transforming Growth Factor beta/metabolism


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