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A distinct subset of attenuated CD8+ T cells that retain crucial cytotoxic functions has been identified in chronic hepatitis B infection and linked to viral control.
In this paper and the related paper from Lugli and colleagues the authors show that high levels of NaCl inside the tumor have a beneficial effect on CD8+ T cells and their ability to control tumor growth as a result of enhanced T cell receptor activity.
Heim et al. investigate the role of CD8+ T cells specific to HBV polymerase in the context of chronic HBV infection. They identify a unique subset of CD8+ T cells with an attenuated effector function. The attenuation is driven by TGFβ signaling, offering new insights into the immune landscape of chronic HBV infection and suggesting potential therapeutic avenues for modulating these cells to enhance viral control.
Along with a back-to-back published paper from Zielisnki and co. in this issue of Nature Immunology, this paper shows that NaCl affects CD8+ T cell function by counteracting the exhaustion of these cells in the tumor microenvironment.
Seder and colleagues review the latest scientific advances in understanding how monoclonal antibodies to the circumsporozoite protein prevent malaria and highlight how this emerging intervention can be used alone or alongside existing antimalarial interventions to control malaria across at-risk populations.
Here the authors present a mass cytometry-based method for identification of antigen-specific T cells and their differentiation state, testing it in cancer, bacterial and viral mouse models.
HIV-specific CD8+ T cells are dysfunctional in the majority of people living with HIV. However, long-term treatment with antiretroviral therapy may considerably improve the antiviral function of these cells.
Here the authors provide a resource for ovarian cancer combining spatial transcriptomics, genomics, CRISPR Perturb-seq screens and in silico methods to focus on T cells and natural killer cells in the tumor and their role in immune evasion.
Appay and colleagues show that long-term antiretroviral therapy is associated with clonal succession of HIV-1-specific CD8+ T cell populations, which evolved from an exhaustion-like toward a stemness-like phenotype.
By use of a degron-mediated acute protein degradation model, Schwickert and colleagues are able to distinguish between direct and indirect gene targets of multiple transcription factors involved in early B cell development.
Profiling of T cell responses in the lungs of patients with pneumonia revealed that early and persistent enrichment of T cells correlates with survival from SARS-CoV-2 pneumonia. Notably, lung T cells with an interferon-stimulated profile and specific for SARS-CoV-2 structural proteins support survival, whereas those that gain a nuclear factor-κB (NF-κB)-driven inflammatory profile and are directed against nonstructural proteins were associated with poor clinical outcomes.
The AIRE protein drives the expression of tissue-restricted self-antigens, required to induce immune tolerance for self-proteins. New work shows the importance of an external interaction between AIRE and the transcriptional activator CBP/p300, and an internal competition for nuclear-condensate formation.
Sun Hur and colleagues examine the mechanism of Aire protein function underlying peripheral tissue antigen gene expression in thymic mTECs. They show that Aire condensates assemble on enhancers that are subject to intricate regulatory mechanisms, ensuring tight coordination of Aire CARD polymerization with genomic target recognition.
Tumor immunoediting occurs early during tumorigenesis and is thereby difficult to study. Here the authors overcome this issue using an aggressive breast cancer model that enables them to compare and contrast the trancriptomic state of early versus late tumors.
Longitudinal sampling of human lymph nodes using fine-needle aspiration after influenza or SARS-CoV-2 vaccination reveals substantial durability and transcriptional reprogramming of follicular helper T cells over time.
Mudd, Ellebedy and colleagues integrate single-cell transcriptomics and TCR sequencing to characterize the spike-specific CD4+ TFH cell response in the lymph nodes and blood of BNT162b2-vaccinated and SARS-CoV-2-infected individuals up to 6 months after vaccination or infection.
Schattgen et al. profiled the subsets and clonality of CD4+ TFH cells in the blood and lymph nodes of human volunteers who received two influenza vaccines 1 year apart to characterize their dynamics and clonal evolution over 2 years.