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IDO AND CD40 MAY BE KEY MOLECULES FOR IMMUNOSUPPRESSIVE CAPACITY OF THE PRIMED TONSIL-DERIVED MESENCHYMAL STEM CELLS
DEPARTMENT OF OTORHINOLARYNGOLOGY-HEAD AND NECK SURGERY, CHUNCHEON SACRED HEART HOSPITAL, HALLYM UNIVERSITY COLLEGE OF MEDICINE
HYUN-JOO LEE, DONG-KYU KIM
¸ñÀû: Recently, tonsil-derived mesenchymal stem cells (T-MSCs) were reported to have characteristics of MSC and had a suppressive effect on T cells, yet much remains unknown about the underlying mechanisms that support this effect. Therefore, we investigated the underlying mechanism of immunomodulatory effect for T-MSCs on immune cell proliferation and cytokine production. ¹æ¹ý:We isolated T-MSCs from human palatine tonsil and evaluated the immunomodulatory capacity using RT-PCR, ELISA, and flow cytometry. In addition, we assessed the expression of various soluble factors and several costimulatory molecules to detect the priming effect on T-MSCs. °á°ú:We found that T-MSCs suppressed the T cell proliferation in a dose- dependent manner. T-MSCs also significantly inhibited the immune cell proliferation and cytokine expression (TNF- and IFN-) in the direct co-culture, but there was no suppressive effect in indirect co- culture. Additionally, we detected a remarkably higher expression of indoleamine 2,3-dioxygenase (IDO) in the primed T-MSCs having co- expression CD40. Moreover, CD4+T cells showed lower TNF-¥á, IFN-¥ã, and IL-4 expression when the primed T-MSC added; whereas those findings were reversed when the inhibitor for IDO or CD40 were added. However, there was no rescued IL-4 expression on the addition of IDO inhibitor. Furthermore, T-bet and GATA3 levels were significantly decreased in the co-cultures of the primed T-MSCs and CD4+T cells; whereas those findings were reversed when we added the neutralizing anti-CD40 antibody. °á·Ð:Our study suggest that the primed T-MSCs expressing IDO and CD40 may have immunomodulatory capacity via not only Th1-mediated immune response but also Th2-mediated immune response.


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