Reviews & Analysis

Zhang et al. describe how meningeal MAIT cells maintain meningeal barrier integrity via the secretion of antioxidants, which also limit neuroinflammation and preserve spatial learning.

The bacillus Calmette–Guérin (BCG) vaccine induces homotypic protection against tuberculosis and, surprisingly, heterotypic protection against other pathogens. New work shows that BCG vaccination causes leakage of microbial gut metabolites into circulation, which induces changes in alveolar macrophages protective against pneumonia.

Understanding immune determinants of vaccine-mediated immunogenicity could further provide rational vaccine design. Two research groups revealed pre-existing and early innate immune signatures associated with better vaccine-mediated antibody responses.

Mechanisms that explain the hygiene hypothesis for allergy and asthma are unclear. A mouse model that cohouses ‘dirty’ pet-store mice with clean laboratory mice might help to understand this immunology.

DNSe, a double-negative thymocyte-specific Notch1 enhancer, is essential for activation of Notch1 expression and has a central role in T-cell-lineage commitment during the earliest stages of thymocyte development.

An enduring antibody response is ultimately dependent on the generation and maintenance of long-lived plasma cells. New research describes the use of single-cell transcriptomics approaches to reveal the defining features of longevity in plasma cells.

Clonal expansion and immunological memory of lymphocytes provide protective immunity against repeated pathogen exposure in mammals. New technologies are enabling the investigation of these intricate processes, focusing on human natural killer cells during human cytomegalovirus infection.

Effective vaccines elicit neutralizing antibodies and long-lasting memory, but this can be challenging with some pathogens, such as HIV. A new study shows how a slow-delivery protein immunization strategy administered in dose-escalation format over 12 days increased the durability of germinal centers and improved immunological outcomes.

CD40 has long been known as a co-stimulatory molecule involved in T cell help for dendritic cells, and thereby as a contributor to CD8⁺ T cell immunity against cancers and infections. However, CD40 signaling drives complex functional responses that can contribute to tumor-specific CD8⁺ T cell responses in unexpected ways.

Akin to adult stem cells, precursor exhausted T cells are hierarchically organized, with long-lived CD62L⁺ stem-like T cells at the apex of the system. The transcription factor c-Myb controls the formation, maintenance and therapeutic function of these cells, with important implications for their clinical utilization.

Current SARS-CoV-2 vaccine recipients differ in infection history and the magnitude of their elicited antibody response. A large human cohort distinguished by these parameters are queried for effector T cell subsets, memory B cells and ability to recognize epitopes from SARS-CoV-2 variants of concern.

m1A58 is a common tRNA modification that can influence protein translational efficiency. Here Liu et al. reveal that tRNA methylation controls in vivo T cell activation by enhancing translation of the key transcription factor Myc.

A key biochemical event that enables T cells to discriminate between TCR antigens of varying affinities and to respond only to high-affinity antigens is full activation of the kinase ZAP70.

ETS1 regulates tissue-remodeling properties of specific fibroblast subtypes in the synovium, gut and cancer and thus emerges as a novel cross-tissue therapeutic target for modulation of pathogenic fibroblast activation.

The net effect of type I interferon (IFN-I) signaling on tumor control depends on various factors, including the potential engagement of adaptive anticancer immunity. New findings delineate a targetable epigenetic mechanism by which suboptimal IFN-I signaling promotes tumor progression in the context of cancer stem cell expansion and immunoevasion.

The inhibitory checkpoint molecule CTLA-4 is essential for regulatory T cell function. A new study highlights the differential manner in which CTLA-4 binds CD80 and CD86, which determines its cellular fate and orchestrates immune tolerance regulation.

Wherry and colleagues describe how anti-PD-1 immunotherapy impacts outcomes of influenza vaccination in patients with cancer, and specifically, how it increases seroconversion and affects quantitative and qualitative aspects of antibodies and follicular T helper cell responses.

Multistep mechanosensing of lymphocyte infiltration and proliferation by the remodeling stroma and matrix underlies the immensely rapid and massive tissue expansion by lymph nodes in response to immune challenge.

Specific brain circuits recruited during stress contribute to differential immune responses and affect how the immune system handles viral and autoimmune challenges.

Immune checkpoint blocking therapies do not always work and come with some risks, but identifying non-responders and patients at risk of adverse events is becoming easier and more accurate.