title: 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.
authors.affiliation: Transplant Unit, Kyoto University Hospital, Kyoto, Japan. jk1640@kuhp.kyoto-u.ac.jp
authors.forename: Jun
authors.initials: J
authors.lastname: Kanamune
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Iwanaga
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kina
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Noguchi
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Matsumura
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.forename: Suong-Hyu
authors.initials: SH
authors.lastname: Hyon
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006086:Graft vs Host Disease / Q000188:drug therapy*; D016867:Immunocompromised Host; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology; D059808:Polyphenols / Q000494:pharmacology / Q000627:therapeutic use*; D013154:Spleen / Q000166:cytology / Q000637:transplantation; D013662:Tea / Q000737:chemistry*
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D015704:CD4 Antigens; D007376:Interleukin-2; D008934:Mitogens; D059808:Polyphenols; D013662:Tea; D007371:Interferon-gamma; D002392:Catechin; C045651:epigallocatechin gallate