IL-7 improves the T cell IFNγ response in sepsis patients

Le résumé fourni par la source

Abstract Sepsis is the life-threatening organ dysfunction stemming from the severe inflammatory response to systemic microbial infection. Immune consequences for post-septic survivors include acute lymphopenia and prolonged susceptibility to infection. Stratifying Patient Immune Endotypes in Sepsis (‘SPIES’) is a prospective observational study testing the utility of ELISpot as a bioassay to identify the immunosuppressed endotype, and test potential immune stimulants for clinical use. Our data show a whole blood IFNγ ELISpot assay can identify: 1) septic patients at increased risk of late mortality, and 2) immunosuppressed sepsis patients. We wanted to determine which cells in the blood were producing IFNγ. Flow cytometry revealed memory CD4 and CD8 T cells were making the majority of IFNγ after ex vivo stimulation with anti-CD3/CD28 mAb. We next defined the breadth of cytokines produced by whole blood samples from sepsis patients after stimulation. Last, we tested the potential for IL-7 to improve the functional activity of T cells from sepsis patients. Using anti-CD3/CD28 mAb-stimulated PBMC from healthy and septic donors, we found adding IL-7 to the stimulation milieu improves both the number of cytokine-producing cells, and magnitude/variety of cytokines produced from T cells. In sum, these data reveal important functional information about the degree of immune suppression experienced by sepsis patients, along with a potential means of restoring T cell function in these patients.

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