ババ ノブヤス
  馬場 伸育
   所属   川崎医科大学  医学部 基礎医学 免疫学
   職種   講師
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 CD47(low) status on CD4 effectors is necessary for the contraction/resolution of the immune response in humans and mice.
掲載誌名 正式名:PloS one
略  称:PLoS One
ISSNコード:19326203/19326203
掲載区分国外
巻・号・頁 7(8),pp.e41972
著者・共著者 Vu Quang Van, Nobuyasu Baba, Manuel Rubio, Keiko Wakahara, Benoit Panzini, Carole Richard, Genevieve Soucy, Denis Franchimont, Genevieve Fortin, Ana Carolina Martinez Torres, Lauriane Cabon, Santos Susin, Marika Sarfati
発行年月 2012/08
概要 How do effector CD4 T cells escape cell death during the contraction of the immune response (IR) remain largely unknown. CD47, through interactions with thrombospondin-1 (TSP-1) and SIRP-α, is implicated in cell death and phagocytosis of malignant cells. Here, we reported a reduction in SIRP-α-Fc binding to effector memory T cells (T(EM)) and in vitro TCR-activated human CD4 T cells that was linked to TSP-1/CD47-induced cell death. The reduced SIRP-α-Fc binding (CD47(low) status) was not detected when CD4 T cells were stained with two anti-CD47 mAbs, which recognize distinct epitopes. In contrast, increased SIRP-α-Fc binding (CD47(high) status) marked central memory T cells (T(CM)) as well as activated CD4 T cells exposed to IL-2, and correlated with resistance to TSP-1/CD47-mediated killing. Auto-aggressive CD4 effectors, which accumulated in lymph nodes and at mucosal sites of patients with Crohn's disease, displayed a CD47(high) status despite a high level of TSP-1 release in colonic tissues. In mice, CD47 (CD47(low) status) was required on antigen (Ag)-specific CD4 effectors for the contraction of the IR in vivo, as significantly lower numbers of Ag-specific CD47(+/+)CD4 T cells were recovered when compared to Ag-specific CD47(-/-) CD4 T cells. In conclusion, we demonstrate that a transient change in the status of CD47, i.e. from CD47(high) to CD47(low), on CD4 effectors regulates the decision-making process that leads to CD47-mediated cell death and contraction of the IR while maintenance of a CD47(high) status on tissue-destructive CD4 effectors prevents the resolution of the inflammatory response.
DOI 10.1371/journal.pone.0041972
PMID 22870271