Abstract
TRAIL-dependent suppression of naïve and memory CD8 T cell responses to secondary bacterial infection after sepsis (99.14)
The Journal of immunology (1950), Vol.186(1_Supplement), pp.99-99.14
04/01/2011
DOI: 10.4049/jimmunol.186.Supp.99.14
Abstract
Abstract Sepsis is the leading cause of death in most ICUs, and the death of septic patients usually does not result from the initial septic event but rather from subsequent nosocomial infections. Patients who survive severe sepsis often display severely compromised immune function. Using a cecal-ligation and puncture (CLP) model to induce intra-abdominal polymicrobial peritonitis, we recently established a link between the apoptotic cells generated during sepsis and the induction of sepsis-induced immune suppression. Using a clinically-relevant “two-hit” sepsis model that better reflects the delayed mortality seen during sepsis due to secondary infection, we have extended this work to investigate sepsis-induced immune suppression of naïve and memory Ag-specific CD8 T cell responses to an experimental heterologous bacterial (LM-OVA) infection. CLP-treated WT mice had a reduced ability to clear LM-OVA vs. sham-treated WT mice, which was paralleled by suppressed T cell responses in the CLP-treated mice. In contrast, bacterial clearance and T cell responses were similar in CLP- and sham-treated TRAIL-/- and DR5-/- mice. Administration of a blocking anti-TRAIL mAb to CLP-treated WT mice led to bacterial clearance and T cell responses like those seen in sham-treated mice. These data further suggest the importance of TRAIL in the induction of sepsis-induced immune suppression and that TRAIL neutralization may be a potential therapeutic target to restore cellular immunity in septic patients.
Details
- Title: Subtitle
- TRAIL-dependent suppression of naïve and memory CD8 T cell responses to secondary bacterial infection after sepsis (99.14)
- Creators
- Thomas GriffithPrajwal GurungDeepa RaiVladimir Badovinac
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.186(1_Supplement), pp.99-99.14
- DOI
- 10.4049/jimmunol.186.Supp.99.14
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 04/01/2011
- Academic Unit
- Infectious Diseases; Internal Medicine; Pathology
- Record Identifier
- 9984362739702771
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