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Immunomodulation of Delayed-Type Hypersensitivity Responses by Mesenchymal Stem Cells Is Associated with Bystander T Cell Apoptosis in the Draining Lymph Node

Cited 31 time in Web of Science Cited 35 time in Scopus
Authors
Lim, Jong-Hyung; Kim, Jung-Sik; Yoon, Il-Hee; Shin, Jun-Seop; Yang, Seung-Ha; Park, Chung-Gyu; Kim, Sang-Joon; Nam, Hye-Young
Issue Date
2010-10-01
Publisher
AMER ASSOC IMMUNOLOGISTS
Citation
JOURNAL OF IMMUNOLOGY; Vol.185 7; 4022-4029
Abstract
Disease amelioration by mesenchymal stem cells (MSCs) has been shown to be closely related to their immunomodulatory functions on the host immune system in many disease models. However, the underlying mechanisms of how these cells affect the immune cells in vivo are not fully understood. In this study, we report findings that a small but significant number of MSCs accumulate in the secondary lymphoid organs and attenuate delayed-type hypersensitivity (DTH) response by inducing apoptotic cell death of surrounding immune cells in the draining lymph node (LN). In the migration study, i.v. infused GFP-MSCs preferentially accumulated at the boundary between the paracortical area and the germinal center in the LNs, in close proximity to various types of immune cells including T, B, and dendritic cells in a dose-dependent manner. As a result, accumulated MSCs markedly attenuated DTH response in proportion to the number of MSCs infused. During the DTH response, the infiltration of T cells in the challenged site was significantly decreased, whereas a number of apoptotic T cells were remarkably increased in the draining LN. Apoptosis was significantly induced in activated T cells (CD3(+) and BrdU(+)), but not in the resting T cells (CD3(+) and BrdU(+)). NO was associated with these apoptotic events. Taken together, we conclude that significant numbers of i.v. infused MSCs preferentially localize in the draining LN, where they induce apoptosis of the activated T cells by producing NO and thus attenuate the DTH response. The Journal of Immunology, 2010, 185: 4022-4029.
ISSN
0022-1767
Language
English
URI
http://hdl.handle.net/10371/76937
DOI
https://doi.org/10.4049/jimmunol.0902723
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College of Medicine/School of Medicine (의과대학/대학원)Microbiology (미생물학전공)Journal Papers (저널논문_미생물학전공)
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