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CD47Low Status on CD4 Effectors Is Necessary for the Contraction/Resolution of the Immune Response in Humans and Mice.
- Source :
- PLoS ONE; Aug2012, Vol. 7 Issue 8, Special section p1-10, 10p
- Publication Year :
- 2012
-
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<subscript>EM</subscript>) 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<superscript>low</superscript> 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<superscript>high</superscript> status) marked central memory T cells (T<subscript>CM</subscript>) 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<superscript>high</superscript> status despite a high level of TSP-1 release in colonic tissues. In mice, CD47 (CD47<superscript>low</superscript> status) was required on antigen (Ag)-specific CD4<superscript>+/+</superscript> effectors for the contraction of the IR in vivo, as significantly lower numbers of Ag-specific CD47<subscript>+/+</subscript>CD4 T cells were recovered when compared to Ag-specific CD47<subscript>-/-</subscript> CD4T cells. In conclusion, we demonstrate that a transient change in the status of CD47, i.e. from CD47<superscript>high></superscript> to CD47<superscript>low</superscript>, 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]
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 8
- Database :
- Complementary Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 80433990
- Full Text :
- https://doi.org/10.1371/journal.pone.0041972