IL-7 promotes T cell viability, trafficking, and functionality and improves survival in sepsis

Jacqueline Unsinger, Margaret McGlynn, Kevin R. Kasten, Andrew S. Hoekzema, Eizo Watanabe, Jared T. Muenzer, Jacquelyn S. McDonough, Johannes Tschoep, Thomas A. Ferguson, Jonathan E. McDunn, Michel Morre, David A. Hildeman, Charles C. Caldwell, Richard S. Hotchkiss

Research output: Contribution to journalArticlepeer-review

231 Scopus citations

Abstract

Sepsis is a highly lethal disorder characterized by widespread apoptosis-induced depletion of immune cells and the development of a profound immunosuppressive state. IL-7 is a potent antiapoptotic cytokine that enhances immune effector cell function and is essential for lymphocyte survival. In this study, recombinant human IL-7 (rhIL-7) efficacy and potential mechanisms of action were tested in a murine peritonitis model. Studies at two independent laboratories showed that rhIL-7 markedly improved host survival, blocked apoptosis of CD4 and CD8 T cells, restored IFN-γ production, and improved immune effector cell recruitment to the infected site. Importantly, rhIL-7 also prevented a hallmark of sepsis (i.e., the loss of delayed-type hypersensitivity), which is an IFN-γ- and T cell-dependent response. Mechanistically, rhIL-7 significantly increased the expression of the leukocyte adhesion markers LFA-1 and VLA-4, consistent with its ability to improve leukocyte function and trafficking to the infectious focus. rhIL-7 also increased the expression of CD8. The potent antiapoptotic effect of rhIL-7 was due to increased Bcl-2, as well as to a dramatic decrease in sepsis-induced PUMA, a heretofore unreported effect of IL-7. If additional animal studies support its efficacy in sepsis and if current clinical trials continue to confirm its safety in diverse settings, rhIL-7 should be strongly considered for clinical trials in sepsis.

Original languageEnglish
Pages (from-to)3768-3779
Number of pages12
JournalJournal of Immunology
Volume184
Issue number7
DOIs
StatePublished - Apr 1 2010

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