1. Regulatory KIR+RA+ T cells accumulate with age and are highly activated during viral respiratory disease
- Author
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Teun Guichelaar, Daan K. J. Pieren, Josine van Beek, Rimke J Postel, Rob Mariman, Noortje A. M. Smits, Vinitha Kandiah, Jelle de Wit, Debbie van Baarle, and Jeroen Hoeboer
- Subjects
0301 basic medicine ,Male ,Aging ,Population ,killer‐cell immunoglobulin‐like receptors ,Biology ,CD8-Positive T-Lymphocytes ,medicine.disease_cause ,CD8+ T cells ,Virus ,regulatory T cells ,03 medical and health sciences ,0302 clinical medicine ,Receptors, KIR ,T-Lymphocyte Subsets ,Influenza, Human ,medicine ,Cytotoxic T cell ,Humans ,Respiratory system ,education ,Receptor ,respiratory viral infection ,Coronavirus ,Aged ,Aged, 80 and over ,education.field_of_study ,Original Paper ,SARS-CoV-2 ,Respiratory disease ,COVID-19 ,Cell Biology ,Original Articles ,Middle Aged ,medicine.disease ,030104 developmental biology ,Gene Expression Regulation ,Immunology ,T‐cell activation ,Female ,viral respiratory disease ,030217 neurology & neurosurgery ,CD8 - 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., Viral infectious diseases such as influenza especially affect the older population due to immunological dysfunctions. We describe a new aging‐related subset of CD8+ T cells that is identified by the co‐expression of KIR and CD45RA and expresses features of senescence/exhaustion and immune suppression. This T‐cell subset increases with age and comprises a major part of the T cells that become activated during influenza correlating with disease in older persons, indicating clinical relevance.
- Published
- 2021