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 |
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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 |