Increased T‐bet is associated with senescence of influenza virus‐specific CD8 T cells in aged humans. Issue 6 (25th February 2013)

• Record Type: Journal Article
• Authors: Dolfi, Douglas V.; Mansfield, Kathleen D.; Polley, Antonio M.; Doyle, Susan A.; Freeman, Gordon J.; Pircher, Hanspeter; Schmader, Kenneth E.; Wherry, E. John
• Is Part Of: Journal of leukocyte biology. Volume 93:Issue 6(2013)
• Page Start: 825
• Page End: 836
• Publication Date: 2013-02-25
• Subjects: CD57 -- PD‐1 -- KLRG‐1 -- Eomes -- CD107 -- exhaustion; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.0912438
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Increased T‐bet levels and senescence in CD8 T cells from aged individuals as possible mechanisms for decreased influenza‐specific functionality. 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.