Murine Mesenchymal Stem Cells Suppress T Lymphocyte Activation Through IL-2 Receptor α (CD25) Cleavage by Producing Matrix Metalloproteinases

Min Jung Park, Jun Seop Shin, Yong Hee Kim, So Hee Hong, Seung Ha Yang, Jin Young Shin, Su Young Kim, Bongi Kim, Jung Sik Kim, Chung Gyu Park

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Mesenchymal stem cells (MSCs) are multipotent, non-hematopoietic stem cells that exhibit the capacity to inhibit the proliferation of a variety of immune cells. However, the underlying mechanisms of the immunosuppressive effects of MSCs are still obscure. Therefore, we attempted to identify the mechanisms underlying immunosuppression toward the activated T lymphocytes by MSCs in a murine model. In particular, we aimed to find possible factors derived from MSCs that drive this phenomenon. We found that T lymphocytes incubated with conditioned media of MSCs (MSC CM) entered into apoptosis and were subjected to cell cycle arrest during the course of activation, and these phenomena were accompanied by the reduction of IL-2 production. Specifically, matrix metalloproteinases (MMPs) derived from MSCs caused cleavage of IL-2 receptor α (CD25) from the surface of activated T cells, and as a consequence, IL-2 signaling in response to engagement of the IL-2 receptor (IL-2R) was downregulated. The inhibition of MMP activity in the MSC CM by GM6001 abrogated CD25 cleavage and restored IL-2 production from the activated splenocytes. However, the blockade of MMP activity could not fully restore the proliferative response and apoptosis of T cells altered by MSC CM. In conclusion, MSC-derived MMPs have a significant role in the suppression of IL-2 production through induction of CD25 cleavage and have a partial role in the suppression of T cell proliferation.

Original languageEnglish
Pages (from-to)381-393
Number of pages13
JournalStem Cell Reviews and Reports
Issue number2
StatePublished - Jun 2011

Bibliographical note

Funding Information:
Acknowledgement This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (Project No. A040004).


  • Apoptosis
  • CD25 cleavage
  • Cell cycle arrest
  • Matrix metalloproteinases
  • Mouse mesenchymal stem cells
  • T cell suppression


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