News & Views

The use of T cell receptor signatures to track activated spike-specific T cell dynamics between recovery from SARS-CoV-2 infection and subsequent mRNA vaccination shows that vaccination effectively recruits pre-existing memory and new CD8⁺ T cell clonotypes.

Epithelial cells, macrophages and T cells are linked in a previously unknown regulatory circuit. Sensing of interferon-γ triggers antigen presentation by colonic epithelial cells, enabling T cells to lower extracellular ATP levels and reduce inflammation.

Expressing chimeric antigen receptors (CARs) in macrophages has led to promising results in preclinical and clinical work. Now, induced pluripotent stem cells have been combined with a second-generation CAR to achieve macrophage rewiring and to broaden the applicability of the approach to solid malignancies.

T cells exist in many functional states, and dynamic transitions from one state to another affect the outcome of adoptive T cell therapy. FOXP1 and KLF2 are now identified as transcriptional regulators of the stemness of CD8⁺ CAR-T cells and the bifurcation of stem-like CD8⁺ CAR-T cells into effector and exhausted subsets, respectively.

BCG vaccination provides protection against unrelated viral infections. The vaccine induces protective integrated organ immunity through biphasic activation of innate and adaptive immune cells.

The immune response to dengue virus infection is a well-coordinated balancing act. New research shows that an imbalanced response — driven partially by the productive infection of antigen-presenting cells — is associated with progression to severe disease.

Regulatory T (T_reg) cells maintain the balance between immune protection and pathology. Research has now found that intestinal T_reg cells produce IL-27 to restrain T_H17 cell-mediated immune responses, effectively restricting autoimmune inflammation and limiting T cell responses to certain gut pathogens.

Determining the immune crosstalk between macrophages and NK cells in bronchioalveolar lavage fluid during SARS-CoV-2 infection in macaques identifies immunoregulatory properties of NK cells and their implications for viral persistence.

S100A8 and S100A9 are cytosolic alarmins with autocrine functions that facilitate neutrophil recruitment. Rapid, transient gasdermin-D pore formation is now shown to mediate secretion of these proteins in response to E-selectin without driving pyroptosis.

Two new studies in which apoE expression in mice is manipulated provide insights into the roles of microglial apoE in neurodegeneration.

Severe COVID-19 is marked by excessive inflammation that can persist after infection. The commensal yeast Candida albicans is now implicated in the acute and chronic immunopathology of COVID-19.

Hogan et al. identify a co-immunodominant influenza peptide presented in mice by MHC-E, a nonclassical class I molecule. Notably, the peptide derives from a 16-residue alternative reading frame translated by leaky ribosome scanning of the M1 mRNA and is recognized by conventional CD8⁺ T cells.

Immune checkpoint inhibitors provide beneficial anti-tumor immunity but risk immune-related adverse events occurring in normal tissues. Notably, selective deletion of PGLYRP1, a protein expressed by several immune cells, protects against tumor cell growth and autoimmunity.

For decades, beta-blockers have been used widely to treat cardiovascular diseases. Surprisingly, new data show how these inhibitors can also improve immunotherapy against tumors and chronic infections.

After vaccination, spike-specific CD8⁺ T cells play an important part in the immediate immune response to breakthrough SARS-CoV-2 infection, whereas the B cell and neutralizing antibody responses come into effect 2 weeks after infection.

Many transcription factors contain intrinsically disordered regions whose functions are not well characterized. An intrinsically disordered region in TCF-1 has now been found to have an essential function in coordinating T cell lineage commitment.

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.