Increased T-bet is associated with senescence of influenza virus-specific CD8 T cells in aged humans

Journal of Leukocyte Biology

Antonio M. Polley⁴  Susan A. Doyle³  Hanspeter Pircher¹  Douglas V. Dolfi⁴  Kathleen D. Mansfield⁴  E. John Wherry⁴  Gordon J. Freeman²  Kenneth E. Schmader  and³ 

[1] Department of Immunology, University of Freiburg, Freiburg, Germany Institute for Immunology, Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA;Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; Division of Geriatrics, Department of Medicine, Duke University Medical Center, and Geriatric Research, Education and Clinical Center, Durham, North Carolina, USA;Institute for Immunology, Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA;

关键词: CD57;    PD-1;    KLRG-1;    Eomes;    CD107;    exhaustion;   

DOI  :  10.1189/jlb.0912438

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown