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

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.

KIR-HLA interactions extend human CD8+ T cell lifespan in vivo

“…Mechanisms within this category include NK cell interactions with dendritic cells which subsequently affect T cell responses during priming (14), NK killing of activated CD4 + and CD8 + T cells (10)(11)(12) and suppression of T cells by a recently-described population of iKIR-expressing regulatory CD8 + T cells (15,16).…”

Senescent T cells: Beneficial and detrimental roles

“…For example, during SARS-CoV-2, 151,152 Influenza B, 152 or Seasonal coronavirus, 152 the frequency of T cells within CD4 + and CD8 + compartments that express CD57 and KIR or EMRA and inflammation increase significantly in the lungs compared to uninfected individuals.…”

The adaptive immune system in early life: The shift makes it count

“…Moreover, TVM cells have been shown to contribute to the control of HIV-infected CD4 + T cells in humans, likely through KIR-mediated interactions and killing of infected cells ( 101 ). Furthermore, our group has recently shown that KIR-expressing TVM cells accumulate in the blood with progressing age and are capable of suppressing proliferation of other CD8 + T cells ( 102 ). Based on these findings, TVM cells may also be considered a type of suppressive CD8 + T-cell subset, although their role at early age remains to be elucidated.…”