title: CD47(low) status on CD4 effectors is necessary for the contraction/resolution of the immune response in humans and mice.
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 (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-α-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.
authors.affiliation: Immunoregulation Laboratory, Centre Hospitalier de l'Université de Montréal, Research Center (CRCHUM), Notre-Dame Hospital, Montreal, Quebec, Canada.
authors.forename: Vu Quang
authors.initials: VQ
authors.lastname: Van
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Baba
authors.forename: Manuel
authors.initials: M
authors.lastname: Rubio
authors.forename: Keiko
authors.initials: K
authors.lastname: Wakahara
authors.forename: Benoit
authors.initials: B
authors.lastname: Panzini
authors.forename: Carole
authors.initials: C
authors.lastname: Richard
authors.forename: Genevieve
authors.initials: G
authors.lastname: Soucy
authors.forename: Denis
authors.initials: D
authors.lastname: Franchimont
authors.forename: Genevieve
authors.initials: G
authors.lastname: Fortin
authors.forename: Ana Carolina Martinez
authors.initials: AC
authors.lastname: Torres
authors.forename: Lauriane
authors.initials: L
authors.lastname: Cabon
authors.forename: Santos
authors.initials: S
authors.lastname: Susin
authors.forename: Marika
authors.initials: M
authors.lastname: Sarfati
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D051928:CD47 Antigen / Q000235:genetics / Q000276:immunology*; D016923:Cell Death / Q000235:genetics; D017637:Clonal Deletion; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology
chemical_list: D000943:Antigens, Differentiation; D051928:CD47 Antigen; C497894:CD47 protein, human; C497895:Cd47 protein, mouse; C508594:IL2 protein, human; D007376:Interleukin-2; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic; C501920:SIRPA protein, human