Regulatory KIR+RA+ T cells accumulate with age and are highly activated during viral respiratory disease

DKJ Pieren, NAM Smits, J Hoeboer, V Kandiah… - Aging …, 2021 - Wiley Online Library
DKJ Pieren, NAM Smits, J Hoeboer, V Kandiah, RJ Postel, R Mariman, J van Beek
Aging Cell, 2021Wiley Online Library
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 …
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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