| First Author | Van VQ | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 8 | Pages | e41972 |
| PubMed ID | 22870271 | Mgi Jnum | J:189662 |
| Mgi Id | MGI:5446826 | Doi | 10.1371/journal.pone.0041972 |
| Citation | Van VQ, et al. (2012) CD47(low) status on CD4 effectors is necessary for the contraction/resolution of the immune response in humans and mice. PLoS One 7(8):e41972 |
| abstractText | 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-alpha, is implicated in cell death and phagocytosis of malignant cells. Here, we reported a reduction in SIRP-alpha-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-alpha-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-alpha-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. |
