Reviews & Analysis

The transcription factor NFAT5 regulates T cell exhaustion, a dysfunctional state caused by chronic exposure to antigen and other signals, during cancer but not during chronic viral infection.

IRF4 is required for the differentiation of T cells, B cells and some myeloid cells. A new study finds that IRF4 is upregulated following natural killer (NK) cell activation and is required for the differentiation and expansion of virus-specific NK cells by controlling nutrient acquisition, including iron uptake.

A recent study identified a microglia–T cell communication axis that retains CD8⁺ T cells in brains with amyloid pathology. Data from this study indicate that CD8⁺ T cells restrict Alzheimer’s disease pathogenesis.

Control of the alternative commitment of immature CD4⁺CD8⁺ T cells to the CD4⁺ or CD8⁺ lineage has long been the subject of intense scrutiny. A combination of CITE-seq and functional assays provides significant new insights into the distinct T cell antigen receptor signaling requirements for these lineage fates.

A recent study shows how intratumoral glutamine supplementation can improve the function of tumor-infiltrating dendritic cells and enhance the CD8⁺ T cell anti-tumor response.

Malaria is a vector-borne disease caused by Plasmodium parasites. In an exciting new study, Ganley et al. harness the power of mRNA vaccines to summon tissue-resident memory T cells to battle the parasite as it replicates in the liver.

The functional heterogeneity of macrophages has ontological and microenvironmental bases, and differentially affects pathology. In pancreatitis, tissue-resident macrophages promote protective fibrosis that favors the maintenance of pancreatic homeostasis. In pancreatic ductal adenocarcinoma, they promote tumor progression by facilitating stromal desmoplasia.

The first detailed investigation of CD8⁺ tumor-infiltrating T cell differentiation in the hours after cells enter a tumor has yielded an unexpected twist. Naive T cells veer away from effector fate and enter the path towards exhaustion much earlier than expected.

Bronchus-associated lymphoid tissue (BALT), which develops in the lung during infancy before declining over childhood, supports localized immune reactions against airway infections in early life including the generation of germinal center-like B cells specific for respiratory pathogens.

Delineation of the steps that lead to immune-related adverse effects indicates that checkpoint-mediated suppression of autoreactive T cells occurs within peripheral target tissues rather than at the point of lymph node activation.

Despite the absence of MHC class II molecules on tumor cells, stem-cell-like CD4⁺ T cells specific for tumor neoantigens can mediate profound antitumor effects by licensing antigen-presenting cells and augmenting antitumor CD8⁺ T cells in the tumor microenvironment and draining lymph nodes.

Confusion exists as to whether transitional dendritic cells are a bone fide subset or just a transitional state, as the name indicates. New data are complicating matters further by showing some interesting heterogeneity in these cells.

CD8⁺ virtual memory T cells have been studied mainly for their antimicrobial functions but it seems that their descendants can contribute to inflammation and hair loss in the context of alopecia areata.

Naive B cells activated during infection enter the germinal center (GC) reaction, in which high-affinity antibodies are generated. A new study has uncovered a distinct metabolic requirement for B cells poised to undergo the GC reaction, whose activation required lactate dehydrogenase A-dependent aerobic glycolysis.

COVID-19 vaccines have been successful, but their duration and level of protection could be improved to cover all SARS-CoV-2 variants. A self-assembling enveloped virus-like particle vaccine combining features of mRNA and protein vaccines might provide a way forward.

Single-cell RNA sequencing distinguishes subsets of fibroblastic reticular cells and predicts pathways that support immune function via crosstalk with lymphocytes.

Presentation of signal peptides by HLA-E to natural killer cells prevents cell lysis via interactions with the inhibitory CD94–NKG2A receptor. A study now reveals an unexpected level of sophistication and heterogeneity in this receptor–ligand interaction.

Indigenous populations are disproportionately affected by COVID-19, but are rarely studied. An investigation of the immune response of Australian First Nations people to SARS-CoV-2 vaccination and infection shows a major effect of comorbidities.

In mice and humans, changes in neutrophil phenotypes and functionality during aging aggravate thromboinflammation in ischemic brain injury and determine the pathology associated with strokes. In mice, inhibition of CXCL3 signaling and rejuvenation of bone marrow offer ways of restricting brain injury and improving stroke outcomes.

Bystander activation that leads to expression of IL-9 in effector T_H9 cells is induced by a TCR-independent, STAT-dependent mechanism and may represent a new strategy for therapeutic intervention to treat T_H9-induced pathologies in vivo.