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STAT5 phosphorylation in T cell subsets from septic patients in response to recombinant human interleukin-7: a pilot
Julie Demaret1, Guillaume Dupont1, Fabienne Venet1
1*Immunology Laboratory and Intensive Care Units, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France; Centre hospitalier universitaire de Saint-Etienne, Intensive Care Units, Saint-Etienne, France; and Hospices Civils de Lyon, Centre hospitalier Lyon-Sud, Intensive Care Units, Pierre Bénite, France.
Abstract:
Septic shock is characterized by lymphocyte alterations associated with increased risk of nosocomial infections and mortality. IL-7, a cytokine required for T cell survival, is thought as a novel therapy for septic patients with severe lymphopenia. We assessed CD4(+) lymphocyte responsiveness to rhIL-7 in septic shock patients ex vivo. Thirteen septic shock patients and 10 controls were included. The MFI of pSTAT5, a key signaling molecule for IL-7, was measured by flow cytometry in CD4(+)FOXP3- (Teffs) and CD4(+)FOXP3(+) (Tregs) lymphocytes after whole-blood incubation with increasing doses of rhIL-7. The basal level of pSTAT5 in nonstimulated T cells was higher in patients. However, the maximal activation level in response to the highest doses of rhIL-7 was similar in both groups. Importantly, low doses of rhIL-7 preferentially activated Teff versus Treg in patients and nonsurvivors tended to present with decreased pSTAT5 expression. This pilot study is the first to highlight, in septic patients, the interest of pSTAT5 measurement in whole blood for the monitoring of rhIL-7 therapy. Such a method could represent an innovative, biologic tool for monitoring leukocyte pharmacological responses to biotherapies in daily clinical practice in other clinical contexts.
Insights
Interleukin-7 (IL-7) therapy shows potential for septic shock patients with lymphopenia. Measuring phosphorylated STAT5 (pSTAT5) in T cells ex vivo can monitor treatment response and patient outcomes.
Area of Science:
- Immunology
- Critical Care Medicine
- Molecular Biology
Background:
- Septic shock involves lymphocyte alterations, increasing infection risk and mortality.
- Interleukin-7 (IL-7) supports T cell survival and is a potential therapy for septic lymphopenia.
Purpose of the Study:
- To assess CD4+ lymphocyte responsiveness to recombinant human IL-7 (rhIL-7) in septic shock patients.
- To evaluate pSTAT5 as a biomarker for rhIL-7 therapy monitoring in septic patients.
Main Methods:
- Ex vivo whole-blood incubation of lymphocytes from 13 septic shock patients and 10 controls with rhIL-7.
- Flow cytometry measurement of phosphorylated STAT5 (pSTAT5) in CD4+ FOXP3- (Teff) and CD4+ FOXP3+ (Treg) cells.
- Analysis of pSTAT5 signaling in response to varying rhIL-7 doses.
Main Results:
- Septic shock patients had higher basal pSTAT5 levels but similar maximal activation to rhIL-7 compared to controls.
- Low rhIL-7 doses preferentially activated Teff cells over Treg cells in septic patients.
- Non-survivors showed a trend towards decreased pSTAT5 expression.
Conclusions:
- pSTAT5 measurement in whole blood is a promising tool for monitoring rhIL-7 therapy in septic patients.
- This method could be adapted for monitoring leukocyte responses to biotherapies in clinical practice.
