Here the authors use a tonsil organoid culture model system to investigate the roles of human CD4⁺ and CD8⁺ regulatory T cells in controlling self-reactive immune responses. CD4⁺ regulatory T cells were stronger regulators of autoreactive B cells, autoantibodies and antigen-specific antibody affinity, whereas CD8⁺ regulatory T cells predominantly controlled expansion of follicular helper cells and autoreactive CD4⁺ and CD8⁺ T cells.

To mature, dendritic cells collect and synthesize cholesterol to construct lipid nanodomains on their membranes. Obstructing this process impairs their ability to prime T cells.

Ordovas-Montanes and colleagues describe the composition of the nasal cellular ecosystem and signatures of disease severity in vaccinated and unvaccinated adults during infection with the ancestral, Delta and Omicron variants of SARS-CoV-2.

Adoro and colleagues report the involvement of the IRE1α–XBP1 signaling axis in protecting hematopoietic stem and progenitor cells from proteomic stress and as a safeguard against leukemic transformation.

To mature, dendritic cells collect and synthesize cholesterol to construct lipid nanodomains on their membranes. Obstructing this process impairs their ability to prime T cells.

Ordovas-Montanes and colleagues describe the composition of the nasal cellular ecosystem and signatures of disease severity in vaccinated and unvaccinated adults during infection with the ancestral, Delta and Omicron variants of SARS-CoV-2.

Here the authors use a tonsil organoid culture model system to investigate the roles of human CD4⁺ and CD8⁺ regulatory T cells in controlling self-reactive immune responses. CD4⁺ regulatory T cells were stronger regulators of autoreactive B cells, autoantibodies and antigen-specific antibody affinity, whereas CD8⁺ regulatory T cells predominantly controlled expansion of follicular helper cells and autoreactive CD4⁺ and CD8⁺ T cells.

Here the authors show that, in mouse tumors, CD8⁺ T cells with a low-avidity TCR are the mediators of antitumor and immunotherapy responses, in part because T cells with a high-avidity TCR are more exhausted.

Adoro and colleagues report the involvement of the IRE1α–XBP1 signaling axis in protecting hematopoietic stem and progenitor cells from proteomic stress and as a safeguard against leukemic transformation.

Divangahi and colleagues report that β-glucan pretreatment before influenza A virus challenge can increase survival by inducing long-term reprogramming of neutrophils, promoting disease tolerance irrespective of viral load.

Here I propose the ‘Creation Game’, inspired by the Turing test, to assess the capacity of artificial intelligence for human-like creativity, focusing on its potential for scientific discovery about the human immune system in the field of systems vaccinology.