Journal article
Pathogen-Specific Inflammatory Milieux Tune the Antigen Sensitivity of CD8+ T Cells by Enhancing T Cell Receptor Signaling
Immunity (Cambridge, Mass.), Vol.38(1), pp.140-152
01/24/2013
DOI: 10.1016/j.immuni.2012.09.017
PMCID: PMC3557574
PMID: 23260194
Abstract
CD8+ T cells confer host protection through T-cell-receptor (TCR)-mediated recognition of foreign antigens presented by infected cells. Thus, generation of CD8+ T cell populations with high antigen sensitivity is critical for efficient pathogen clearance. Besides selection of high-affinity TCRs, the molecular mechanisms regulating the antigen sensitivity of CD8+ T cells remain poorly defined. Herein, we have demonstrated that the antigen sensitivity of effector and memory CD8+ T cells is dynamically regulated and can be tuned by pathogen-induced inflammatory milieux independently of the selection of cells with higher TCR affinity. Mechanistically, we have demonstrated that the signal-transduction capacity of key TCR proximal molecules is enhanced by inflammatory cytokines, which reduced the antigen density required to trigger antimicrobial functions. Dynamic tuning of CD8+ T cell antigen sensitivity by inflammatory cytokines most likely optimizes immunity to specific pathogens while minimizing the risk of immunopathology at steady state.
► Inflammatory cytokines tune the antigen sensitivity of CD8+ T cells ► Tuning of antigen sensitivity is dynamic and pathogen specific ► Cytokine signaling directly to CD8+ T cells regulates antigen sensitivity ► Inflammatory cytokines enhance TCR signaling of effector and memory CD8+ T cells
Details
- Title: Subtitle
- Pathogen-Specific Inflammatory Milieux Tune the Antigen Sensitivity of CD8+ T Cells by Enhancing T Cell Receptor Signaling
- Creators
- Martin J Richer - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USAJeffrey C Nolz - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USAJohn T Harty - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Immunity (Cambridge, Mass.), Vol.38(1), pp.140-152
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.immuni.2012.09.017
- PMID
- 23260194
- PMCID
- PMC3557574
- ISSN
- 1074-7613
- eISSN
- 1097-4180
- Language
- English
- Date published
- 01/24/2013
- Academic Unit
- Pathology
- Record Identifier
- 9984047612002771
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