Mesenchymal Stem Cells Alter Migratory Property of T and Dendritic Cells to Delay the Development of Murine Lethal Acute Graft-Versus-Host Disease (original) (raw)

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Department of Cell Biology, Institute of Basic Medical Sciences

, Beijing,

China

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Department of Experimental Haematology, Institute of Radiation Medicine

, Beijing,

China

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Department of Cell Biology, Institute of Basic Medical Sciences

, Beijing,

China

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Department of Cell Biology, Institute of Basic Medical Sciences

, Beijing,

China

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Department of Cell Biology, Institute of Basic Medical Sciences

, Beijing,

China

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Department of Cell Biology, Institute of Basic Medical Sciences

, Beijing,

China

Correspondence: Ning Mao, M.D., Department of Cell Biology, Institute of Basic Medical Sciences, 27 Tai-Ping Road, Beijing 100,850, China. Telephone: 8610-68173543; Fax: 8610-68213039; e-mail: maoning@nic.bmi.ac.cn

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Received:

14 February 2008

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Hong Li, ZiKuan Guo, XiaoXia Jiang, Heng Zhu, XiuSen Li, Ning Mao, Mesenchymal Stem Cells Alter Migratory Property of T and Dendritic Cells to Delay the Development of Murine Lethal Acute Graft-Versus-Host Disease, Stem Cells, Volume 26, Issue 10, October 2008, Pages 2531–2541, https://doi.org/10.1634/stemcells.2008-0146
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Abstract

Due to the potent immunoregulatory capacity, mesenchymal stem cells (MSCs) have been used in clinical trials to treat acute graft-versus-host disease (aGvHD), although the detailed in vivo mechanisms remain elusive. In a murine lethal aGvHD model, MSCs delayed the development of the disease. Interestingly, we found that MSC infusion increased the number of T lymphocytes in the secondary lymphoid organs (SLOs). Since the expression of CD62L and CCR7 is prerequisite for lymphocyte migration into SLOs, the in vitro experiments revealed that in the presence of MSCs, T lymphocytes (including CD4+CD25+ regulatory T cells) preferred to take the naive-like phenotype (CD62L+/CCR7+) in mixed lymphocyte reaction and maintained the migratory activity elicited by secondary lymphoid tissue chemokine (SLC). Dendritic cells (DCs) are the initiator of immune response. CCR7 expression is pivotal for their maturation and migration into SLOs. However, CCR7 expression and SLC-driven migratory activity of DCs were remarkably suppressed by MSC coculture. The processes above were realized mainly through secretory mechanism. Consistently, MSC infusion maintained T lymphocytes to take CD62L+/CCR7+ phenotype and decreased the CCR7 expression and proportion of DCs in SLOs of aGvHD mice. In conclusion, the altered migratory properties of T cells and DCs might contribute to the immunosuppressive activity of transplanted MSCs in the setting of aGvHD.

Disclosure of potential conflicts of interest is found at the end of this article.

Copyright © 2008 AlphaMed Press

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open\_access/funder\_policies/chorus/standard\_publication\_model)

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