tetano
Editor, Senior Moderator
J Leukoc Biol. 2013 Feb 25. [Epub ahead of print]
Increased T-bet is associated with senescence of influenza virus-specific CD8 T cells in aged humans.
Dolfi DV, Mansfield KD, Polley AM, Doyle SA, Freeman GJ, Pircher H, Schmader KE, Wherry EJ.
Source
*Institute for Immunology, Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA;
Abstract
Aged individuals have increased morbidity and mortality following influenza and other viral infections, despite previous exposure or vaccination. Mouse and human studies suggest increased senescence and/or exhaustion of influenza virus-specific CD8 T cells with advanced age. However, neither the relationship between senescence and exhaustion nor the underlying transcriptional pathways leading to decreased function of influenza virus-specific cellular immunity in elderly humans are well-defined. Here, we demonstrate that increased percentages of CD8 T cells from aged individuals express CD57 and KLRG1, along with PD-1 and other inhibitory receptors, markers of senescence, or exhaustion, respectively. Expression of T-box transcription factors, T-bet and Eomes, were also increased in CD8 T cells from aged subjects and correlated closely with expression of CD57 and KLRG1. Influenza virus-specific CD8 T cells from aged individuals exhibited decreased functionality with corresponding increases in CD57, KLRG1, and T-bet, a molecular regulator of terminal differentiation. However, in contrast to total CD8 T cells, influenza virus-specific CD8 T cells had altered expression of inhibitory receptors, including lower PD-1, in aged compared with young subjects. Thus, our data suggest a prominent role for senescence and/or terminal differentiation for influenza virus-specific CD8 T cells in elderly subjects.
PMID:
23440501
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23440501
Increased T-bet is associated with senescence of influenza virus-specific CD8 T cells in aged humans.
Dolfi DV, Mansfield KD, Polley AM, Doyle SA, Freeman GJ, Pircher H, Schmader KE, Wherry EJ.
Source
*Institute for Immunology, Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA;
Abstract
Aged individuals have increased morbidity and mortality following influenza and other viral infections, despite previous exposure or vaccination. Mouse and human studies suggest increased senescence and/or exhaustion of influenza virus-specific CD8 T cells with advanced age. However, neither the relationship between senescence and exhaustion nor the underlying transcriptional pathways leading to decreased function of influenza virus-specific cellular immunity in elderly humans are well-defined. Here, we demonstrate that increased percentages of CD8 T cells from aged individuals express CD57 and KLRG1, along with PD-1 and other inhibitory receptors, markers of senescence, or exhaustion, respectively. Expression of T-box transcription factors, T-bet and Eomes, were also increased in CD8 T cells from aged subjects and correlated closely with expression of CD57 and KLRG1. Influenza virus-specific CD8 T cells from aged individuals exhibited decreased functionality with corresponding increases in CD57, KLRG1, and T-bet, a molecular regulator of terminal differentiation. However, in contrast to total CD8 T cells, influenza virus-specific CD8 T cells had altered expression of inhibitory receptors, including lower PD-1, in aged compared with young subjects. Thus, our data suggest a prominent role for senescence and/or terminal differentiation for influenza virus-specific CD8 T cells in elderly subjects.
PMID:
23440501
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23440501