Cd31 is required on cd4+ T cells to promote T cell survival during salmonella infection

Ewan A. Ross, Ruth E. Coughlan, Adriana Flores-Langarica, Saeeda Bobat, Jennifer L. Marshall, Khiyam Hussain, James Charlesworth, Nikita Abhyankar, Jessica Hitchcock, Cristina Gil, Constantino Loṕez-Maciás, Ian R. Henderson, Mahmood Khan, Steve P. Watson, Ian C.M. MacLennan, Christopher D. Buckley*, Adam F. Cunningham

*Corresponding author for this work

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1553-1565
Number of pages13
JournalJournal of Immunology
Volume187
Issue number4
DOIs
Publication statusPublished - 15 Aug 2011

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    Ross, E. A., Coughlan, R. E., Flores-Langarica, A., Bobat, S., Marshall, J. L., Hussain, K., Charlesworth, J., Abhyankar, N., Hitchcock, J., Gil, C., Loṕez-Maciás, C., Henderson, I. R., Khan, M., Watson, S. P., MacLennan, I. C. M., Buckley, C. D., & Cunningham, A. F. (2011). Cd31 is required on cd4+ T cells to promote T cell survival during salmonella infection. Journal of Immunology, 187(4), 1553-1565. https://doi.org/10.4049/jimmunol.1000502