Attenuation of murine GVHD by a tea polyphenol

Authors: Jun Kanamune, Tatsuo Kina, Yasuhiro Iwanaga, Hirofumi Noguchi, Kazuaki Matsumura, Shinji Uemoto, Suong-Hyu Hyon

Source: Cell Transplantation

Publisher: Cognizant Communication Corporation

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Abstract:

Since donor T-cells' allorecognition of host antigens is a prerequisite prerequisite for the onset of graft versus host disease (GVHD), blocking their cellular signaling pathways can decrease the severity of GVHD. We hypothesized that epigallocatechin-3-gallate (EGCG), due to its strong affinity to macromolecules, would adhere to surface molecules of donor T-cells, inhibit their allorecognition and attenuate GVHD in the recipient. We tested the hypothesis by treating donor splenocytes with EGCG in both in vitro and in vivo murine GVHD models. EGCG treatment decreased the proliferation of donor cells in MLR cultures and secretion of IL-2 and INF-γ. It also reduced the epitope detection of CD3ε, CD4 and CD28 but did not down-regulate the protein expression of these molecules, suggesting blockage of cell surface stimulatory signals. Similarly, EGCG treatment did not decrease mRNA expression for some of these molecules but decreased mitogen-induced cell proliferation, indicating that EGCG did not interfere the transcription of these genes but affected cell proliferation pathways. Furthermore, EGCG-treated donor splenocytes when transplanted into immunocompromized recipient mice decreased of proliferation, and the treatment extended the recipients' survival at least during the early stage of GVHD. These results strongly suggest that EGCG attenuates by both blocking specific cell surface molecules the donor T-cells' proliferation pathways.

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DOI: http://dx.doi.org/10.3727/096368911X623934

Appeared or available online: February 13, 2012