Reviews & Analysis

The use of T cell receptor signatures to track activated spike-specific T cell dynamics between recovery from SARS-CoV-2 infection and subsequent mRNA vaccination shows that vaccination effectively recruits pre-existing memory and new CD8⁺ T cell clonotypes.

Epithelial cells, macrophages and T cells are linked in a previously unknown regulatory circuit. Sensing of interferon-γ triggers antigen presentation by colonic epithelial cells, enabling T cells to lower extracellular ATP levels and reduce inflammation.

Expressing chimeric antigen receptors (CARs) in macrophages has led to promising results in preclinical and clinical work. Now, induced pluripotent stem cells have been combined with a second-generation CAR to achieve macrophage rewiring and to broaden the applicability of the approach to solid malignancies.

T cells exist in many functional states, and dynamic transitions from one state to another affect the outcome of adoptive T cell therapy. FOXP1 and KLF2 are now identified as transcriptional regulators of the stemness of CD8⁺ CAR-T cells and the bifurcation of stem-like CD8⁺ CAR-T cells into effector and exhausted subsets, respectively.

We describe a system for introducing guide RNAs (gRNAs) to Cas9-expressing hematopoietic stem cells, which are used to generate mice with gene knockouts in the immune system. By using different gRNA-containing vectors and Cas9-expressing mice, we created systems for knockout of single genes or pairs of genes constitutively or inducibly.

BCG vaccination provides protection against unrelated viral infections. The vaccine induces protective integrated organ immunity through biphasic activation of innate and adaptive immune cells.

Mouse macrophages express specialized genes particular to the organs they inhabit, but whether the same applies in humans is unclear. In human peritoneal fluid, we identified many macrophage phenotypes, including two specialized macrophage types that corresponded to distinct mouse peritoneal macrophages. However, their abundances were markedly different between species.

In this Review, Netea and colleagues summarize the latest research that contributes to our understanding of the pathophysiology of sepsis, and how this contributes to a new treatment approach through personalized immunotherapy.

In this Review, the authors describe the mechanisms that account for the generation and immune recognition of neoantigens that are not derived from DNA mutations, with a special focus on relevance to cancer and autoimmunity.