CD31 is required on CD4+ T cells to promote T cell survival during Salmonella infection

• Published in: The Journal of immunology (1950) 2011-08, Vol.187 (4), p.1553-1565
• Main Authors: Ross, Ewan A, Coughlan, Ruth E, Flores-Langarica, Adriana, Bobat, Saeeda, Marshall, Jennifer L, Hussain, Khiyam, Charlesworth, James, Abhyankar, Nikita, Hitchcock, Jessica, Gil, Cristina, López-Macías, Constantino, Henderson, Ian R, Khan, Mahmood, Watson, Steve P, MacLennan, Ian C M, Buckley, Christopher D, Cunningham, Adam F
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Apoptosis - genetics; Apoptosis - immunology; Cell Survival - genetics; Cell Survival - immunology; Inflammation - genetics; Inflammation - immunology; Inflammation - microbiology; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Mice; Platelet Endothelial Cell Adhesion Molecule-1 - genetics; Platelet Endothelial Cell Adhesion Molecule-1 - immunology; Salmonella; Salmonella - genetics; Salmonella - immunology; Salmonella Infections - genetics; Salmonella Infections - immunology; Th1 Cells - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1000502

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.