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.

We isolated CD4⁺ T cell clones from healthcare workers infected with SARS-CoV-2 during the first COVID-19 wave and identified 21 epitopes across three viral proteins: spike, membrane and nucleoprotein. Focusing on spike protein, for seven of ten epitopes mutated in variants of concern, we found that T cell recognition was impaired.

The fungal pathogen receptor dectin-1 instructs the development of non-pathogenic T_H17 cells via TGFβ activation. This process requires strict control of the expression of type I interferon to ensure a delicate balance in the expression of its effector genes that control the release of active TGFβ.

Cohousing pet-store mice with laboratory mice leads to the natural transfer of microbes and subsequent inflammation in laboratory mice. Lung group 2 innate lymphoid cells — rapid responders to airway allergens — are transiently inhibited by inflammatory signals, but their activity recovers once the active infection subsides.

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.

The US National Institute of Allergy and Infectious Diseases (NIAID) convened a virtual workshop in July 2022 to address the research landscape and identify gaps and opportunities in the understanding of durable vaccine protection.

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.

Halper-Stromberg and Jabri discuss the molecular and functional adaptations to inflammatory or pathogenic stimuli that shape the immune identity of each individual.

Godbout and colleagues discuss the neuroimmune mechanisms that underlie social-stress defeat, anxiety, and post-traumatic stress disorder.

By combining single-cell mRNA sequencing and a genetic pulse–chase mouse model, we identified multiple subsets of mouse long-lived plasma cells and showed that these cells can originate from diverse developmental routes.

A stage-specific enhancer augments Notch1 signaling from the early thymic progenitor (ETP) through double-negative thymocyte stages. Enhanced Notch1 activity is required for T cell lineage differentiation at the later end of this developmental interval, but Notch1 also suppresses precocious T lineage commitment in ETPs and promotes their expansion as multi-lineage progenitors.

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.

We identified the transmembrane protein CMTM4 as an essential component of the IL-17 receptor. CMTM4 is required for membrane expression of IL-17 receptor subunit C and activation of IL-17A pro-inflammatory signaling. Lack of CMTM4 largely protects mice from experimental psoriasis, which suggests that targeting CMTM4 might alleviate IL-17-mediated autoimmunity.

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.