title: Frontline Science: Placenta-derived decidual stromal cells alter IL-2R expression and signaling in alloantigen-activated T cells.
abstract: This study investigated how stromal cells affect the IL-2 pathway in alloantigen-activated T cells. We found that decidual stromal cells (DSCs) from term placentas promoted a high production of IL-2 in cultures with alloantigen-activated T cells. The intensity of expression of cluster of differentiation 25 (CD25; IL-2Rα) on T cells was increased by DSCs, whereas the frequency and intensity of expression of the signaling subunits CD122 (IL-2Rβ) and CD132 (IL-2Rγc) were reduced. Consequently, uptake of IL-2 and STAT5 phosphorylation (pSTAT5) was abrogated. DSCs also decreased the proportion of pSTAT5+T cells in response to IL-15, which also use CD122 for signaling. Addition of DSCs to the allogeneic cultures did not increase the expression of programmed death 1 (PD-1) or CD95, indicating that they did not promote T cell exhaustion. However, exogenous recombinant (r)IL-2 in similar concentrations in the same setting increased the expression of CD95 and down-regulated CD122 in T cells. The antiproliferative effect of sirolimus (SRL) and cyclosporine A (CsA), which target the IL-2 signaling pathway, was diminished by DSCs in vitro. To conclude, DSCs affect IL-2 production and IL-2R expression and signaling, which may contribute to the stromal cell-mediated immune modulation and phenotype shift seen in activated T cells. Altered proliferation in cultures when combining DSCs and SRL or CsA may be of clinical importance, as stromal cells are used in trials for acute inflammation and are often used in combination with conventional immunosuppressive therapies.
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; tom.erkers@ki.se.
authors.forename: Tom
authors.initials: T
authors.lastname: Erkers
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.|Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Huddinge, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Solders
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lotte
authors.initials: L
authors.lastname: Verleng
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bergström
authors.affiliation: Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Arwen
authors.initials: A
authors.lastname: Stikvoort
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.|Department of Clinical Science, University of Bergen, Bergen, Norway; and.
authors.forename: Lalit
authors.initials: L
authors.lastname: Rane
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Silvia
authors.initials: S
authors.lastname: Nava
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.|Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Huddinge, Sweden.
authors.forename: Helen
authors.initials: H
authors.lastname: Kaipe
mesh_terms: D003656:Decidua / Q000166:cytology*; D015536:Down-Regulation / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D020033:Protein Isoforms / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D007519:Isoantigens; D020033:Protein Isoforms; D021122:Protein Subunits; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor
keywords: GVHD; HSCT; STAT5; immune regulation; immune suppression