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.
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