Regulatory KIR RA T cells accumulate with age and are highly activated during viral respiratory disease.
Pieren, Daan K J Smits, Noortje A M Hoeboer, Jeroen Kandiah, Vinitha Postel, Rimke J Mariman, Rob van Beek, Josine van Baarle, Debbie de Wit, Jelle Guichelaar, Teun
Pieren, Daan K J
Smits, Noortje A M
Hoeboer, Jeroen
Kandiah, Vinitha
Postel, Rimke J
Mariman, Rob
van Beek, Josine
van Baarle, Debbie
de Wit, Jelle
Guichelaar, Teun
Citations
Altmetric:
Series / Report no.
Open Access
Type
Article
Language
en
Date of publication
2021-05-27
Year of publication
Research Projects
Organizational Units
Journal Issue
Title
Regulatory KIR RA T cells accumulate with age and are highly activated during viral respiratory disease.
Translated Title
Published in
Aging Cell 2021; e13372
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.