トキタ ダイスケ   TOKITA Daisuke
  時田 大輔
   所属   医学部 医学科(東京女子医科大学病院)
   職種   教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Suppressive efficacy and proliferative capacity of human regulatory T cells in allogeneic and xenogeneic responses.
掲載誌名 正式名:Transplantation
略  称:Transplantation
ISSNコード:15346080/00411337
掲載区分国外
巻・号・頁 86(10),pp.1452-62
著者・共著者 Lin Yih-Jyh, Hara Hidetaka, Tai Hao-Chih, Long Cassandra, Tokita Daisuke, Yeh Peter, Ayares David, Morelli Adrian E, Cooper David K C
発行年月 2008/11
概要 BACKGROUND:An understanding of the mechanisms that suppress the human anti-pig cellular response is key for xenotransplantation. We have compared the ability of human regulatory T cells (Tregs) to suppress xenogeneic and allogeneic responses in vitro.METHODS:Human peripheral blood mononuclear cells (PBMC), CD4+ T cells, or CD4+ CD25- T cells were stimulated with irradiated human or wild type (WT) or alpha1,3-galactosyltransferase gene-knockout (GT-KO) pig PBMC in the presence or absence of human CD4+ CD25 high Tregs. In separate experiments, 5- (and 6)-carboxyfluorescein diacetate succinimidyl ester-labeled human CD4+ T cells were stimulated with human or pig PBMC. The expansion and precursor frequencies of allo- and xenoreactive Tregs were assessed by labeling with FoxP3 mAb and flow cytometric analysis.RESULTS:The responses of human PBMC, CD4+ T cells, and CD4+ CD25- T cells to pig PBMC were stronger than to human PBMC (P<0.05). Human anti-GT-KO responses were weaker than anti-WT responses (P<0.05). Human CD4+ CD25 high Tregs suppressed proliferation of CD4+ CD25- T cells to both human and pig PBMC stimulator cells with the same efficiency. Alloreactive CD4+ CD25+ FoxP3 high responder T cells proliferated more than their xenoreactive counterparts (P<0.05), although xenoreactive CD4+ CD25+ T cells proliferated more than alloreactive cells (P<0.05). There was no difference in precursor frequency between allo- and xeno-reactive CD4+ CD25+ FoxP3 high cells.CONCLUSIONS:Human T-cell responses to pig cells are stronger than to allogeneic cells. The human response to GT-KO PBMC is weaker than to WT PBMC. Although human Tregs can suppress both responses, expansion of CD4+ CD25+ FoxP3 high cells against pig PBMC is weaker than against human PBMC. More human Tregs may be required to suppress the stronger xenogeneic response.
DOI 10.1097/TP.0b013e318188acb0
PMID 19034017