CD47Low status on CD4 effectors is necessary for the contraction/resolution of the immune response in humans and mice

8Citations
Citations of this article
26Readers
Mendeley users who have this article in their library.

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 (TEM) 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-/- CD4 T 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. © 2012 Van et al.

Cite

CITATION STYLE

APA

Van, V. Q., Baba, N., Rubio, M., Wakahara, K., Panzini, B., Richard, C., … Sarfati, M. (2012). CD47Low status on CD4 effectors is necessary for the contraction/resolution of the immune response in humans and mice. PLoS ONE, 7(8). https://doi.org/10.1371/journal.pone.0041972

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free