Volume 20 Issue 3, March 2019

A multivalent vaccine that presents diverse influenza virus subtype H1 hemagglutinins on its surface induces broadly neutralizing antibodies in an animal model by displaying conserved epitopes at higher density than strain-specific epitopes.

The zinc transporter ZIP7 positively regulates signaling via the BCR during early B cell development in mice and humans. Impairment of ZIP7 function results in a novel primary immunodeficiency.

Combined immunotherapy using checkpoint blockade (anti-CTLA4 and anti-PD-1) and the DPP4 inhibitor sitagliptin reveals the existence of a T cell– and eosinophil-targeted immunotherapy approach for solid tumors.

In patients with rheumatoid arthritis, decreased abundance of the N-myristoyltransferase NMT1 in CD4⁺ T cells prevents N-myristoylation of the AMP-activated protein kinase AMPK and its localization to the lysosomal membrane, which leads to increased activation of the metabolic checkpoint kinase complex mTORC1 and proinflammatory T cell phenotypes.

The transition of the fetus from the womb to the external world represents an extraordinary challenge. The generation of memory T cells before birth may serve an important role in preparation for this fundamental transition.

Eosinophils have been described mainly in allergy settings but are increasingly appreciated as being involved in other aspects of immunity. Albert and colleagues use a clinically approved inhibitor of the dipeptidyl peptidase DPP4 to facilitate the recruitment of eosinophils to mouse tumors, where they are essential in tumor destruction.

Macrophages have important antitumor functions but can be evaded by tumor-expressed CD47-dependent ‘don’t-eat-me’ signals. Beatty and colleagues demonstrate that the Toll-like receptor 9 ligand CpG metabolically reprograms macrophages to overcome don’t-eat-me signals.

Serpins are a large family of serine protease inhibitors. Jae Jung and colleagues show that SERPINB1 serves an endogenous regulatory role for pro-inflammatory caspases by preventing CARD–CARD polymerization and, hence, inflammasome activation.

Tissue-resident memory T cells (T_RM cells) have well-described functions in the protective response to infectious agents. Neurath and colleagues demonstrate that intestinal T_RM cells can also have key pathogenic roles in inflammatory bowel disease.

Koning and colleagues used mass cytometry, single-cell RNA-seq and high-throughput TCR sequencing to characterize the CD4⁺ T cell compartment in the human fetal intestine.

Pathogenic human CD4⁺ T cells in rheumatoid arthritis have hyperactivated metabolism. Weyand and colleagues show that this phenotype is associated with less myristoylation of the energy sensor AMPK and dysregulated metabolic sensor mTORC1.

Exhausted cytotoxic T lymphocytes (CTLs) express the receptor PD-1 as a key signature. Haining and colleagues show that there are different ‘depths’ of exhaustion with a subset of exhausted CTLs that retain polyfunctionality and are responsive to PD-1 blockade.

Stemness is crucial for the maintenance of long-term T cell memory. Gattinoni and colleagues demonstrate that the transcription factor c-Myb is essential for the establishment of a stemness program in the CD8⁺ T cell memory compartment.

Zinc is important for normal immunity but its mechanistic actions are poorly understood. Hambleton and colleagues identify defects in Zn²⁺ transport that underpin a novel human immunodeficiency characterized by loss of mature B cells.

Antigenic variation of influenza A viruses necessitates the annual reformulation of vaccines. Kanekiyo et al. develop a mosaic nanoparticle vaccine against influenza virus that is able to elicit neutralizing antibodies that span nearly 100 years of variation of influenza A virus.