1. CD47Low Status on CD4 Effectors Is Necessary for the Contraction/Resolution of the Immune Response in Humans and Mice.
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Van, Vu Quang, Baba, Nobuyasu, Rubio, Manuel, Wakahara, Keiko, Panzini, Benoit, Richard, Carole, Soucy, Genevieve, Franchimont, Denis, Fortin, Genevieve, Tortes, Ana Carolina Martinez, Cabon, Lauriane, Susin, Santos, Sarfati, Marika, and Hoshino, Yoshihiko
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T cells ,CELL death ,IMMUNE response ,THROMBOSPONDIN-1 ,PHAGOCYTOSIS ,EPITOPES ,CROHN'S disease - Abstract
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 (CD47low 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 (CD47high status) marked central memory T cells (TCM ) 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 CD47high status despite a high level of TSP-1 release in colonic tissues. In mice, CD47 (CD47low 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-/- CD4T cells. In conclusion, we demonstrate that a transient change in the status of CD47, i.e. from CD47high> to CD47low , on CD4 effectors regulates the decision-making process that leads to CD47-mediated cell death and contraction of the IR while maintenance of a CD47high status on tissue-destructive CD4 effectors prevents the resolution of the inflammatory response. [ABSTRACT FROM AUTHOR]- Published
- 2012
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