Frontline Science: Placenta-derived decidual stromal cells alter IL-2R expression and signaling in alloantigen-activated T cells

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

Bergströ¹  Nava, Silvia¹  n, Olle¹  Stikvoort, Arwen¹  Verleng, Lotte³  Kaipe, Helen⁶  Solders, Martin⁶  Rane, Lalit⁶  m, Cecilia⁶  Ringdé⁷ 

[1] and;..Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Huddinge, Sweden;..Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Huddinge, Sweden;..Department of Clinical Science, University of Bergen, Bergen, Norway;Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden;Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden

关键词: HSCT;    immune regulation;    STAT5;    GVHD;    immune suppression;   

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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-2Rγ_c) 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.

【 授权许可】

CC BY