Regulatory KIR+RA+ T cells accumulate with age and are highly activated during viral respiratory disease |
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Authors: | Daan K. J. Pieren Noortje A. M. Smits Jeroen Hoeboer Vinitha Kandiah Rimke J. Postel Rob Mariman Josine van Beek Debbie van Baarle Jelle de Wit Teun Guichelaar |
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Affiliation: | 1. Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven The Netherlands ; 2. Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht The Netherlands |
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Abstract: | Severe respiratory viral infectious diseases such as influenza and COVID‐19 especially affect the older population. This is partly ascribed to diminished CD8+ T‐cell responses a result of aging. The phenotypical diversity of the CD8+ T‐cell population has made it difficult to identify the impact of aging on CD8+ T‐cell subsets associated with diminished CD8+ T‐cell responses. Here we identify a novel human CD8+ T‐cell subset characterized by expression of Killer‐cell Immunoglobulin‐like Receptors (KIR+) and CD45RA (RA+). These KIR+RA+ T cells accumulated with age in the blood of healthy individuals (20–82 years of age, n = 50), expressed high levels of aging‐related markers of T‐cell regulation, and were functionally capable of suppressing proliferation of other CD8+ T cells. Moreover, KIR+RA+ T cells were a major T‐cell subset becoming activated in older adults suffering from an acute respiratory viral infection (n = 36), including coronavirus and influenza virus infection. In addition, older adults with influenza A infection showed that higher activation status of their KIR+RA+ T cells associated with longer duration of respiratory symptoms. Together, our data indicate that KIR+RA+ T cells are a unique human T‐cell subset with regulatory properties that may explain susceptibility to viral respiratory disease at old age. |
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Keywords: | aging, CD8+ T cells, killer‐ cell immunoglobulin‐ like receptors, regulatory T cells, respiratory viral infection, T‐ cell activation, viral respiratory disease |
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