Volume 24 Issue 10, October 2023

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.

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.

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.

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.

On 20–23 June 2023, the 10th International γδ T cell conference was held in Lisbon, Portugal, bringing together basic, translational and clinical researchers studying γδ T cells in health and disease.

We show that multivalent epitope display on the surface of viral-sized particles functions as a ‘stand-alone’ danger signal by evading inhibitory pathways to trigger a unique mode of B cell receptor signaling. The activation, survival and proliferation of B cells stimulated with particulate antigen is highly enhanced compared with those stimulated with soluble antigen, and does not require co-stimulation from T cells.

Glioblastoma is a devastating primary brain tumor consisting of multiple cell populations. We identified TFPI2 as the crucial effector of the symbiotic interaction between glioblastoma stem cells and microglia. Blockade of this symbiosis inhibited tumor growth and synergized with an immune checkpoint inhibitor in mouse models of glioblastoma.

That regulatory T cells can change their phenotypes has been shown in mouse models of atherosclerosis and other autoimmune diseases. We suspected that this phenomenon would also be true in humans. To test this hypothesis, we developed a strategy to identify human ‘exT_reg’ cells and found that they express a cytotoxic transcriptome.

Proal and colleagues review the evidence for long-term persistence of coronavirus SARS-CoV-2 in tissues of infected individuals and discuss how this viral reservoir may contribute to the pathogenesis of post-acute sequelae of COVID-19 (PASC).

Blish and Lee review the response of natural killer cells to SARS-CoV-2 infection.

Verdeil and colleagues show that the transcription factor NFAT5 is selectively required in tumor-induced, but not chronic infection-induced, CD8⁺ T cell exhaustion, possibly due to the modulation of NFAT5 activation by hyperosmolarity in the tumor environment.

Here the authors show that TFPI2 promotes glioblastoma stem cell self-renewal and connects stemness to microglia immunosuppression, plus targeting TFPI2-mediated glioblastoma stem cell–microglia symbiosis inhibits tumor growth and synergizes with anti-PD1 therapy in glioblastoma.

Iron metabolism has been shown to play an important role in the development and function of the immune system, but its role in ILC3s is unclear. Here the authors show that CD71-mediated iron metabolism controls ILC3 proliferation and the host response to Citrobacter rodentium infection and CD71 expression is regulated by Ahr signaling.

Santosa et al. show that IRF4 is upregulated upon NK cell activation and acts as a signal integrator for the differentiation and expansion of mouse cytomegalovirus-specific NK cells by partly controlling nutrient uptake required for adaptive NK cell responses.

The DNA-binding domains of transcription factors have been well characterized, but whether their intrinsically disordered regions control cell fate is unclear. Here, the authors show the functional and mechanistic importance of an intrinsically disordered region of TCF-1 in T cell development.

Wherry and colleagues define the kinetics of vaccine-primed recall immune responses during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection, highlighting rapid activation of memory T cells and broadly enhanced immune responses in previously vaccinated individuals.

Satija and colleagues use multimodal sequencing technologies and cross-modality integration tools to define distinct subpopulations of CD8⁺ T cells that are predictive of COVID-19 severity.

Chi and colleagues identify brain-resident CXCR6⁺PD-1⁺CD8⁺ T cells that interact with resident microglia to limit immune-mediated pathology in a mouse model of Alzheimer’s disease.

In inflammation, some regulatory T (T_reg) cells lose FoxP3 expression and become exT_reg cells. Ley and colleagues mapped mouse T_reg and exT_reg cell transcriptomes to a human peripheral blood mononuclear cell single-cell RNA-sequencing dataset with surface markers (CITE-seq) and identify human exT_reg cells as cytotoxic CD4⁺ T cells.

Zikherman and colleagues uncover a new mechanism by which B cells recognize virus-like antigen display as a stand-alone danger signal (independent of nucleic acid cargo) that does not rely exclusively on avidity and BCR cross-linking.