Umbilical cord-mesenchymal stem cells induce a memory phenotype in CD4+ T cells
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 regene...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1128359/full |
| _version_ | 1827920998281773056 |
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| author | Ezgi Sengun Tim G. A. M. Wolfs Valéry L. E. van Bruggen Bram van Cranenbroek Elles R. Simonetti Daan Ophelders Marien I. de Jonge Irma Joosten Renate G. van der Molen |
| author_facet | Ezgi Sengun Tim G. A. M. Wolfs Valéry L. E. van Bruggen Bram van Cranenbroek Elles R. Simonetti Daan Ophelders Marien I. de Jonge Irma Joosten Renate G. van der Molen |
| author_sort | Ezgi Sengun |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T04:20:42Z |
| format | Article |
| id | doaj.art-628c0e4517bc4fc2802e26f063bd5bdb |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T04:20:42Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-628c0e4517bc4fc2802e26f063bd5bdb2023-06-20T10:10:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.11283591128359Umbilical cord-mesenchymal stem cells induce a memory phenotype in CD4+ T cellsEzgi Sengun0Tim G. A. M. Wolfs1Valéry L. E. van Bruggen2Bram van Cranenbroek3Elles R. Simonetti4Daan Ophelders5Marien I. de Jonge6Irma Joosten7Renate G. van der Molen8Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center Nijmegen, Radboud Institute for Molecular Life Sciences, Nijmegen, NetherlandsDepartment of Pediatrics and GROW School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, NetherlandsDepartment of Pediatrics and GROW School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, NetherlandsDepartment of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center Nijmegen, Radboud Institute for Molecular Life Sciences, Nijmegen, NetherlandsDepartment of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center Nijmegen, Radboud Institute for Molecular Life Sciences, Nijmegen, NetherlandsDepartment of Pediatrics and GROW School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, NetherlandsDepartment of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center Nijmegen, Radboud Institute for Molecular Life Sciences, Nijmegen, NetherlandsDepartment of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center Nijmegen, Radboud Institute for Molecular Life Sciences, Nijmegen, NetherlandsDepartment of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center Nijmegen, Radboud Institute for Molecular Life Sciences, Nijmegen, NetherlandsInflammation 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1128359/fullimmunomodulationumbilical cord mesenchymal stem cellsmemory T cellscentral memoryCD4 + T cellscell contact |
| spellingShingle | Ezgi Sengun Tim G. A. M. Wolfs Valéry L. E. van Bruggen Bram van Cranenbroek Elles R. Simonetti Daan Ophelders Marien I. de Jonge Irma Joosten Renate G. van der Molen Umbilical cord-mesenchymal stem cells induce a memory phenotype in CD4+ T cells Frontiers in Immunology immunomodulation umbilical cord mesenchymal stem cells memory T cells central memory CD4 + T cells cell contact |
| title | Umbilical cord-mesenchymal stem cells induce a memory phenotype in CD4+ T cells |
| title_full | Umbilical cord-mesenchymal stem cells induce a memory phenotype in CD4+ T cells |
| title_fullStr | Umbilical cord-mesenchymal stem cells induce a memory phenotype in CD4+ T cells |
| title_full_unstemmed | Umbilical cord-mesenchymal stem cells induce a memory phenotype in CD4+ T cells |
| title_short | Umbilical cord-mesenchymal stem cells induce a memory phenotype in CD4+ T cells |
| title_sort | umbilical cord mesenchymal stem cells induce a memory phenotype in cd4 t cells |
| topic | immunomodulation umbilical cord mesenchymal stem cells memory T cells central memory CD4 + T cells cell contact |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1128359/full |
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