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For this Viewpoint, Nature Reviews Immunology asked the presidents of 16 immunology societies from around the world to discuss how their society and its members responded to the COVID-19 pandemic. Their answers highlight the incredible contributions that immunologists around the globe have made following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

How can your thymus continue to generate the necessary numbers of CD4⁺CD25⁺ regulatory T (T_Reg) cells once it involutes? Arne Akbar and colleagues propose a model whereby some T_Regcells differentiate from rapidly proliferating memory T cells in the periphery.

Akbar and colleagues show that sestrins induce the reprogramming of non-proliferative, senescent-like CD27^–CD28^–CD8⁺ T cells to acquire an innate-like killing activity modulated by the NK receptor NKG2D and the adaptor molecule DAP12.

Akbar, Lanna and colleagues show that sestrin proteins bind to and coordinate the simultaneous activation of Erk, Jnk and p38 MAPKs in T lymphocytes and inhibit immunity during aging.

Senescent T cells have increased activity of the mitogen-activated protein kinase p38. Akbar and colleagues show that such cells lack the canonical and alternative p38-activation pathways and instead induce kinase AMPK–dependent autophosphorylation of p38.

This article describes the molecular mechanisms involved in T cell senescence and T cell exhaustion, and proposes that these states are controlled by distinct molecular pathways. Blocking exhaustion rather than senescence may be a safer way to enhance immunity to persistent infections and in ageing.

The authors show that cutaneous immunity is attenuated during aging due to the recruitment, by senescent fibroblasts, of inflammatory monocytes, which in turn inhibit resident memory T cell activation. Inhibition of p38 MAPK signaling blocks the recruitment and function of these monocytes and restores immunity.

Senescent cells increase with ageing and may cause inflammatory conditions, but how this accumulation is mediated is still unclear. Here the authors show that senescent cells express HLA-E to suppress NKG2A-mediated natural killer and CD8 T cell activation to avoid targeted elimination, while blocking NKG2A helps promote immunity against senescent cells.

The post-resolution phase of inflammation is not simply a linear path towards cessation of immune response but rather a regulated process involving fluctuating immune activity. Here authors show a pivotal role for post-resolution macrophages in driving a wave of T cell recruitment and activation via prostaglandin E2 and α-integrin signalling during the resolution phase of murine pneumococcal pneumonia.

Bacterial products in the gut–liver axis and tissue stromal factors can tune liver immunity by driving myeloid instruction of CD8⁺ T cells with immunomodulatory ability.

GATA3 has been considered to be primarily associated with CD4⁺ Th2 cell function. Using CD4⁺ effector memory that re-express CD45RA (EMRA) T cells the authors show that in response to DNA damage GATA3 can regulate increase of mitochondrial mass and biogenesis involving AMPK.

Lanna and colleagues discover extracellular vesicle-mediated transfer of telomeres from antigen-presenting cells to T cells, which enables elongation of chromosomes, protection against replicative senescence and long-term immune defence.

Human aging is characterized by an elevated basal inflammatory state. Gilroy and colleagues use a tractable in vivo human inflammation model to demonstrate a mechanism whereby efferocytosis is impaired in the elderly but is reversible by p38 inhibition.

Frailty is an important age-related prognostic for mortality, and little is known about its immune landscape. Luo et al.¹ use single-cell profiling to gather a comprehensive understanding of immune changes that happen from birth to old age, and provide new insights into the often-overlooked state of frailty.

Immune dysfunction increases with age owing to cellular senescence and low-grade inflammation, processes that drive each other during ageing. This Review discusses the potential of therapeutic approaches that target interactions between the tissue environment and the immune system by eliminating senescent cells, inhibiting inflammation and boosting immune function.

Senescent cells and their secretome — the senescence-associated secretory phenotype (SASP) — cause a systemic pro-inflammatory state, contributing to an inflammatory microenvironment. In this article, the authors discuss the presence of senescent cells and the SASP in the ageing prostate and the evidence for a role of senescence in BPH and prostate cancer, as well as possible therapeutic targeting of these pathways in the future.