T cells

Glucocorticoid treatment is used to suppress the immune system in various disease settings. However, endogenous glucocorticoids are able to promote as well as inhibit different aspects of T cell immunity. Here, the authors discuss the many ways in which T cell responses are shaped by glucocorticoids.

Reconstitution of the immune system after depletion by chemotherapy, radiotherapy, infection or transplantation is crucial to maintain protection from infection and to respond to immune-based therapy. Here the authors describe the ways in which a diverse T cell compartment can be restored, focusing on therapeutic strategies that drive the production of new T cells.

A number of T cell-intrinsic peripheral tolerance mechanisms (quiescence, ignorance, anergy, exhaustion, senescence and cell death) restrain autoimmunity and overactive immune responses. Here, the authors provide an integrated perspective of peripheral T cell tolerance by comparing the molecular mechanisms that govern these checkpoints and discussing their role in T cell tolerance and fate regulation.

This Review focuses on the roles of γδ T cells in tissue homeostasis and immune surveillance. The authors discuss exciting new studies showing how γδ T cells can regulate diverse physiological responses in tissues, ranging from thermogenesis in adipose tissue to remodelling at neuronal synapses.

A transcription factor network triggered by Notch signalling in the thymus guides proliferating, multipotent progenitor cells into the T cell pathway. This Review describes how these factors work to establish regulatory target specificity, epigenomic impact and irreversibility for T cell identity.

In this Progress article, Zeyu Chen and E. John Wherry summarize early reports of the T cell responses observed in patients with COVID-19, emphasizing how different immune response characteristics in different patients may reflect a spectrum of disease phenotypes.

The authors compare the thymic development of several innate-like T cell populations, including natural killer T cells, mucosal-associated invariant T cells and γδ T cells. They focus on the cytokines, surface molecules and transcription factors that are necessary for the development of these cells and highlight some of the key differences from conventional T cell development.

This Review covers our current understanding of the roles of IL-9-producing T cells in allergy and cancer. Should these cells be classified as a distinct IL-9-producing T helper cell subset? And can we therapeutically target them for the treatment of chronic allergic diseases and cancer?

The authors describe how the naive T cell compartment is built across a lifetime. They propose that functional diversity among naive T cells is linked to when they were created. Naive T cells adapt to meet changes in the external environment at different stages of life, persist into adulthood and contribute to the T cell compartment in adults.

T cells play a central role in immune responses to cancer. In this guide to cancer immunotherapy, the authors provide a comprehensive historical and biological perspective on cancer immunotherapy, with a focus on current and emerging therapeutic approaches that harness T cells to fight cancer.

Co-inhibitory receptor signalling — through CTLA4, LAG3, PD1, TIGIT, NRP1 and TIM3 — controls the function and stability of regulatory T cells in autoimmunity and cancer and could therefore be amenable to therapeutic targeting.

Recently, antibody-mediated control of HIV infection has received considerable attention. Here, the authors discuss the importance of CD8⁺ T cells in HIV infection and suggest that efforts to develop vaccines that target these cells in conjunction with B cells should be renewed.

Therapies based on adoptive cellular transfer of regulatory T (T_reg) cells are currently undergoing clinical trials for autoimmune diseases, graft-versus-host disease and the prevention of transplant rejection. This Review provides an overview of T_reg cell biology and discusses the latest approaches to enhance T_reg cells for therapeutic purposes.

Recent studies have revealed a specialized population of ‘exhausted’ CD8⁺ T cells that expands on immune checkpoint blockade therapy for cancer and may explain how T cell responses are maintained in chronic conditions. Here, the authors describe their phenotypic, developmental and functional characteristics and why they should be harnessed for successful immunotherapy.

Emerging studies highlight cell metabolism as a crucial regulator of T cell quiescence and activation. This Review describes how immunological cues and nutrients fine-tune metabolic programmes and signalling networks that together promote T cell quiescence exit.

In this Viewpoint article, Nature Reviews Immunology invites 18 experts to discuss the nature of T cell exhaustion. How should T cell exhaustion be defined and what are the developmental relationships between exhausted T cell subsets? The contributors share their thoughts on key recent developments in the field.