Regulatory KIR RA T cells accumulate with age and are highly activated during viral respiratory disease.
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
Author Information
Daan K J Pieren: Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands. ORCID
Noortje A M Smits: Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Jeroen Hoeboer: Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Vinitha Kandiah: Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Rimke J Postel: Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Rob Mariman: Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Josine van Beek: Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Debbie van Baarle: Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Jelle de Wit: Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Teun Guichelaar: Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands. ORCID
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.
