title: CD31 is required on CD4+ T cells to promote T cell survival during Salmonella infection.
abstract: Hematopoietic cells constitutively express CD31/PECAM1, a signaling adhesion receptor associated with controlling responses to inflammatory stimuli. Although expressed on CD4(+) T cells, its function on these cells is unclear. To address this, we have used a model of systemic Salmonella infection that induces high levels of T cell activation and depends on CD4(+) T cells for resolution. Infection of CD31-deficient (CD31KO) mice demonstrates that these mice fail to control infection effectively. During infection, CD31KO mice have diminished numbers of total CD4(+) T cells and IFN-γ-secreting Th1 cells. This is despite a higher proportion of CD31KO CD4(+) T cells exhibiting an activated phenotype and an undiminished capacity to prime normally and polarize to Th1. Reduced numbers of T cells reflected the increased propensity of naive and activated CD31KO T cells to undergo apoptosis postinfection compared with wild-type T cells. Using adoptive transfer experiments, we show that loss of CD31 on CD4(+) T cells alone is sufficient to account for the defective CD31KO T cell accumulation. These data are consistent with CD31 helping to control T cell activation, because in its absence, T cells have a greater propensity to become activated, resulting in increased susceptibility to become apoptotic. The impact of CD31 loss on T cell homeostasis becomes most pronounced during severe, inflammatory, and immunological stresses such as those caused by systemic Salmonella infection. This identifies a novel role for CD31 in regulating CD4 T cell homeostasis.
authors: Medical Research Council Centre for Immune Regulation, School of Immunity and Infection, Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors: Ewan A
authors: EA
authors: Ross
authors: Ruth E
authors: RE
authors: Coughlan
authors: Adriana
authors: A
authors: Flores-Langarica
authors: Saeeda
authors: S
authors: Bobat
authors: Jennifer L
authors: JL
authors: Marshall
authors: Khiyam
authors: K
authors: Hussain
authors: James
authors: J
authors: Charlesworth
authors: Nikita
authors: N
authors: Abhyankar
authors: Jessica
authors: J
authors: Hitchcock
authors: Cristina
authors: C
authors: Gil
authors: Constantino
authors: C
authors: López-Macías
authors: Ian R
authors: IR
authors: Henderson
authors: Mahmood
authors: M
authors: Khan
authors: Steve P
authors: SP
authors: Watson
authors: Ian C M
authors: IC
authors: MacLennan
authors: Christopher D
authors: CD
authors: Buckley
authors: Adam F
authors: AF
authors: Cunningham
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology*; D012475:Salmonella / Q000235:genetics / Q000276:immunology*; D012480:Salmonella Infections / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1