# The changing immune landscape of innate‐like T cells and other innate cells throughout life

## TL;DR

This study explores how innate-like T cells and other innate immune cells change with age, using detailed flow cytometry to compare immune profiles across different life stages.

## Contribution

The study identifies age-related changes in innate-like T cells and introduces CD57 as a universal marker of immune aging.

## Key findings

- Innate-like T cells and other innate immune cells show distinct age-related changes in frequency and phenotype.
- CD57 is identified as a universal maturation marker for both innate and adaptive immune cells during aging.
- ILC3 frequencies peak in young adults, while ILC1 frequencies increase with age.

## Abstract

Spectral flow cytometry is an advanced immunological tool that can enable comprehensive analysis of the immune system by simultaneously comparing innate and adaptive immune cells. Here, using a 40‐color antibody panel, we advance our knowledge of innate‐like cells by investigating chemokine receptors and maturation markers not usually assessed on these populations, examining age‐related effects on these immune cell subsets. We characterize phenotypic changes of peripheral blood mononuclear cells (PBMCs) in three age groups: newborns (cord blood), adults aged 20–30 years, and adults aged > 70 years. We compare the age‐related changes of innate cells, including ILCs, NK cells, monocytes, dendritic cells, and innate‐like T cells, comparing them with memory T cells. We also examine subsets of CD4−CD8− double‐negative (DN) T cells and CD3+CD161+ T cells, revealing they are phenotypically similar to known subsets of innate‐like T cells, and they also increase in frequency in an age‐related manner. The frequencies of ILC1 increased with age, ILC2 remained stable, whereas ILC3 peaked in young adults, and were higher than cord and older adults. Notably, we identify the NK cell maturation marker, CD57, as a universal marker that defines aging populations of both innate and adaptive immune cells. This study enhances our understanding of the ontogeny of human immune cells, highlighting significant age‐related changes in the frequency and phenotype of innate‐like populations of immune cells.

The phenotype of innate‐like T cells changes with age. Here we describe these changes in relation to other subsets of innate cells.