Attenuation of murine graft-versus-host disease by a tea polyphenol.

Abstract:

:Since donor T-cells' allorecognition of host antigens is a 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 CD3ɛ, CD4, and CD28 but did not downregulate 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 GVHD by both blocking specific cell surface molecules and affecting the donor T-cell proliferation pathways.

journal_name

Cell Transplant

journal_title

Cell transplantation

authors

Kanamune J,Iwanaga Y,Kina T,Noguchi H,Matsumura K,Uemoto S,Hyon SH

doi

10.3727/096368911X623934

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

909-18

issue

5

eissn

0963-6897

issn

1555-3892

pii

ct0486kanamune

journal_volume

21

pub_type

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