Umbilical cord-mesenchymal stem cells induce a memory phenotype in CD4+ T cells

Frontiers in Immunology

Immunology

Ezgi Sengun¹  Renate G. van der Molen¹  Bram van Cranenbroek¹  Elles R. Simonetti¹  Marien I. de Jonge¹  Irma Joosten¹  Tim G. A. M. Wolfs²  Daan Ophelders²  Valéry L. E. van Bruggen² 

[1] Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center Nijmegen, Radboud Institute for Molecular Life Sciences, Nijmegen, Netherlands;Department of Pediatrics and GROW School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, Netherlands;

关键词: immunomodulation;    umbilical cord mesenchymal stem cells;    memory T cells;    central memory;    CD4 + T cells;    cell contact;    flow cytometry;   

DOI  :  10.3389/fimmu.2023.1128359

 received in 2022-12-20, accepted in 2023-06-01,  发布年份 2023

来源: Frontiers

【 摘 要 】

Inflammation is a physiological state where immune cells evoke a response against detrimental insults. Finding a safe and effective treatment for inflammation associated diseases has been a challenge. In this regard, human mesenchymal stem cells (hMSC), exert immunomodulatory effects and have regenerative capacity making it a promising therapeutic option for resolution of acute and chronic inflammation. T cells play a critical role in inflammation and depending on their phenotype, they can stimulate or suppress inflammatory responses. However, the regulatory effects of hMSC on T cells and the underlying mechanisms are not fully elucidated. Most studies focused on activation, proliferation, and differentiation of T cells. Here, we further investigated memory formation and responsiveness of CD4+ T cells and their dynamics by immune-profiling and cytokine secretion analysis. Umbilical cord mesenchymal stem cells (UC-MSC) were co-cultured with either αCD3/CD28 beads, activated peripheral blood mononuclear cells (PBMC) or magnetically sorted CD4+ T cells. The mechanism of immune modulation of UC-MSC were investigated by comparing different modes of action; transwell, direct cell-cell contact, addition of UC-MSC conditioned medium or blockade of paracrine factor production by UC-MSC. We observed a differential effect of UC-MSC on CD4+ T cell activation and proliferation using PBMC or purified CD4+ T cell co-cultures. UC-MSC skewed the effector memory T cells into a central memory phenotype in both co-culture conditions. This effect on central memory formation was reversible, since UC-MSC primed central memory cells were still responsive after a second encounter with the same stimuli. The presence of both cell-cell contact and paracrine factors were necessary for the most pronounced immunomodulatory effect of UC-MSC on T cells. We found suggestive evidence for a partial role of IL-6 and TGFβ in the UC-MSC derived immunomodulatory function. Collectively, our data show that UC-MSCs clearly affect T cell activation, proliferation and maturation, depending on co-culture conditions for which both cell-cell contact and paracrine factors are needed.

【 授权许可】

Unknown   
Copyright © 2023 Sengun, Wolfs, van Bruggen, van Cranenbroek, Simonetti, Ophelders, de Jonge, Joosten and van der Molen