Journal article
Sustained and incomplete recovery of naïve CD8+ T-cell precursors after sepsis contributes to impaired CD8+ T-cell responses to infection
The Journal of immunology (1950), Vol.190(5), pp.1991-2000
03/01/2013
DOI: 10.4049/jimmunol.1202379
PMCID: PMC3578009
PMID: 23355736
Abstract
Patients who survive severe sepsis often display compromised immune function with impairment in innate and adaptive immune responses. These septic patients are highly susceptible to ‘secondary’ infections with intracellular pathogens that are usually controlled by CD8
+
T-cells. It is unknown when and if this observed immunoparalysis of CD8
+
T-cell immunity recovers and the long-term consequences of sepsis on the ability of naïve CD8
+
T-cells to respond to subsequent infections are poorly understood. Here, using the CLP mouse model of sepsis we show that sepsis induces a rapid loss of naïve CD8
+
T-cells. However, IL-15-dependent numerical recovery is observed a month after initial septic insult. Numerical recovery is accompanied by IL-15-dependent phenotypic changes where a substantial proportion of naïve (antigen-inexperienced) CD8
+
T-cells display a ‘memory-like’ phenotype (CD44
hi
/CD11a
hi
). Importantly, the impairment of naïve CD8
+
T-cells to respond to viral and bacterial infection was sustained for month(s) after sepsis induction. Incomplete recovery of naïve CD8
+
T-cell precursors was observed in septic mice, suggesting that the availability of naïve precursors contributes to the sustained impairment in primary CD8
+
T-cell responses. Thus, sepsis can result in substantial and long-lasting changes in the available CD8
+
T-cell repertoire affecting the capacity of the host to respond to new infections.
Details
- Title: Subtitle
- Sustained and incomplete recovery of naïve CD8+ T-cell precursors after sepsis contributes to impaired CD8+ T-cell responses to infection
- Creators
- Stephanie A Condotta - Department of Pathology, University of Iowa, Iowa City, IA 52242Deepa Rai - Department of Pathology, University of Iowa, Iowa City, IA 52242Britnie R James - Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota, Minneapolis, MN 55455Thomas S Griffith - Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota, Minneapolis, MN 55455Vladimir P Badovinac - Department of Pathology, University of Iowa, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.190(5), pp.1991-2000
- DOI
- 10.4049/jimmunol.1202379
- PMID
- 23355736
- PMCID
- PMC3578009
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- R01 AI083286 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
- Language
- English
- Date published
- 03/01/2013
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984047604602771
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