4.7 Article

Human mesenchymal stromal cells enhance the immunomodulatory function of CD8+ CD28- regulatory T cells

Journal

CELLULAR & MOLECULAR IMMUNOLOGY
Volume 12, Issue 6, Pages 708-718

Publisher

CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/cmi.2014.118

Keywords

antigens; CD28; CD8-positive T cells; mesenchymal stromal cells; regulatory T cells

Categories

Funding

  1. National Basic Research Program of China [2012CBA01302, 2010CB945400]
  2. National Natural Science Foundation of China [31171398, 81271265, 81425016]
  3. Key Scientific and Technological Projects of Guangdong Province [2007A032100003]
  4. Natural Science Foundation of Guangdong Province [S2013030013305]
  5. Key Scientific and Technological Program of Guangzhou City [201400000003-3, 201300000089, 2010U1-E00551]
  6. Guangdong Department of Science & Technology Translational Medicine Center grant [2011A080300002]

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One important aspect of mesenchymal stromal cells (MSCs)-mediated immunomodulation is the recruitment and induction of regulatory T (Treg) cells. However, we do not yet know whether MSCs have similar effects on the other subsets of Treg cells. Herein, we studied the effects of MSCs on CD8(+) CD28(-) Treg cells and found that the MSCs could not only increase the proportion of CD8(+) CD28(-) T cells, but also enhance CD8(+) CD28(-)T cells' ability of hampering naive CD4(+) T-cell proliferation and activation, decreasing the production of IFN-gamma by activated CD4(+) T cells and inducing the apoptosis of activated CD4(+) T cells. Mechanistically, the MSCs affected the functions of the CD8(+) CD28(-) T cells partially through moderate upregulating the expression of IL-10 and FasL. The MSCs had no distinct effect on the shift from CD8(+) CD28(+) T cells to CD8(+) CD28(-) T cells, but did increase the proportion of CD8(+) CD28(-) T cells by reducing their rate of apoptosis. Insummary, this study shows that MSCs can enhance the regulatory function of CD8(+) CD28(-) Treg cells, shedding new light on MSCs-mediated immune regulation.

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