EurekaMag.com logo
+ Site Statistics
References:
52,725,316
Abstracts:
28,411,598
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

Human mesenchymal stem cells shift CD8+ T cells towards a suppressive phenotype by inducing tolerogenic monocytes


Journal of Cell Science 125(Pt 19): 4640-4650
Human mesenchymal stem cells shift CD8+ T cells towards a suppressive phenotype by inducing tolerogenic monocytes
The mechanisms underlying the immunomodulatory effects of mesenchymal stem cells (MSCs) have been investigated under extreme conditions of strong T cell activation, which induces the rapid death of activated lymphocytes. The objective of this study was to investigate these mechanisms in the absence of additional polyclonal activation. In co-cultures of peripheral mononuclear blood cells with human MSCs (hereafter referred to as hMSCs), we observed a striking decrease in the level of CD8 expression on CD8+ cells, together with decreased expression of CD28 and CD44, and impaired production of IFN-gamma and Granzyme B. This effect was specific to hMSCs, because it was not observed with several other cell lines. Downregulation of CD8 expression required CD14+ monocytes to be in direct contact with the CD8+ cells, whereas the effects of hMSCs on the CD14+ cells were essentially mediated by soluble factors. The CD14+ monocytes exhibited a tolerogenic pattern when co-cultured with hMSCs, with a clear decrease in CD80 and CD86 co-stimulatory molecules, and an increase in the inhibitory receptors ILT-3 and ILT-4. CD8+ cells that were preconditioned by MSCs had similar effects on monocytes and were able to inhibit lymphocyte proliferation. Injection of hMSCs in humanized NSG mice showed similar trends, in particular decreased levels of CD44 and CD28 in human immune cells. Our study demonstrates a new immunomodulation mechanism of action of hMSCs through the modulation of CD8+ cells towards a non-cytotoxic and/or suppressive phenotype. This mechanism of action has to be taken into account in clinical trials, where it should be beneficial in grafts and autoimmune diseases, but potentially detrimental in malignant diseases.


Accession: 053610496

PMID: 22767507

DOI: 10.1242/jcs.108860



Related references

Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T-cell subsets expressing a regulatory/suppressive phenotype. Haematologica 90(4): 516-525, 2005

Mesenchymal stem cells promote mouse breast tumor progression by inducing the suppressive function of myeloid-derived CD11b⁺ Gr1⁺ cells. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 30(8): 785-788, 2014

Mesenchymal stem cells tune the development of monocyte-derived dendritic cells toward a myeloid-derived suppressive phenotype through growth-regulated oncogene chemokines. Journal of Immunology 190(10): 5065-5077, 2013

Granulocyte-macrophage colony-stimulating factor prevents diabetes development in NOD mice by inducing tolerogenic dendritic cells that sustain the suppressive function of CD4+CD25+ regulatory T cells. Journal of Immunology 179(6): 3638-3647, 2007

Mesenchymal stem cells promote a primitive phenotype CD34+c-kit+ in human cord blood-derived hematopoietic stem cells during ex vivo expansion. Cellular & Molecular Biology Letters 18(1): 11-33, 2013

Inducing arsenic-resistance cells with human bone marrow-derived mesenchymal stem cells. Jiepou Xuebao 37(6): 669-672, 2006

Study on the directed inducing process of cartilage cells differentiated from human marrow mesenchymal stem cells. Zhonghua Er Bi Yan Hou Ke Za Zhi 37(2): 137-139, 2003

Differentiation of human fetal mesenchymal stem cells into cells with an oligodendrocyte phenotype. Cell Cycle 8(7): 1069-1079, 2009

The involvement of ERK pathway in the cellular phenotype conversion in human mesenchymal stem cells cocultured with human sweat gland cells. Zhonghua Shao Shang Za Zhi 22(5): 347-350, 2007

Cellular phenotype conversion induced by co-culture of human mesenchymal stem cells cocultured with human sweat gland cells. Zhonghua Yi Xue Za Zhi 85(27): 1885-1889, 2005