Volume 22 Issue 1, January 2021

The similarities and differences between trained immunity and other immune processes are the subject of intense interrogation. Therefore, a consensus on the definition of trained immunity in both in vitro and in vivo settings, as well as in experimental models and human subjects, is necessary for advancing this field of research. Here we aim to establish a common framework that describes the experimental standards for defining trained immunity.

Comprehensive analysis of specific and cross-reactive SARS-CoV-2 epitopes reveals functional T cell responses against specific viral regions in essentially all convalescent individuals and a majority of unexposed donors, demonstrating that cross-reactive responses to COVID-19 are widespread.

Weyand and Goronzy discuss how the progressive loss of immune cell tolerance underlies the immunopathology associated with rheumatoid arthritis.

Mantovani and colleagues report elevated circulating concentrations of the long pentraxin PTX3 in patients with severe COVID-19. Within this cohort, early detection of high PTX3 concentrations emerged as a strong predictor of decreased survival.

Farber and colleagues report distinct antibody responses to SARS-CoV-2 in pediatric cohorts, including those who developed multisystem inflammatory syndrome (MIS-C), and adult COVID-19 cohorts.

Andreakos and colleagues provide a longitudinal study comparing patients with COVID-19 to patients infected with influenza. They report a dysregulated interferon response whereby IFN-λ and type I IFN production were diminished and delayed in patients with COVID-19, exhibiting a response that is ‘untuned’ with other inflammatory cytokines.

Seder and colleagues use a self-assembling nanoparticle vaccine and adjuvant to expand stem-like CD8⁺ T cells and trigger potent antitumor responses.

Stem cell–like memory (T_SCM) CD8⁺ T cells are beneficial in antitumor responses, in part due to their ability to self-renew. Khleif and colleagues demonstrate that inhibition of the kinase MEK in CD8⁺ T cells favors induction of T_SCM and superior antitumor responses.

COVID-19 is often characterized by a hyperinflammatory syndrome. Wang and colleagues show that low levels of IgG fucosylation enhance interactions with activating Fcγ receptors, boosting the inflammatory cytokines associated with severe COVID-19.

SARS-CoV-2-specific CD4⁺ and CD8⁺ T cell epitopes are found in both convalescent patients and virus-naive volunteers and are indicative of heterologous recognition shared with seasonal cold viruses.

Geisbert and colleagues report that African green monkeys infected with the SARS-CoV-2 virus develop disease symptoms that closely resemble those seen in infected humans, making this animal model a useful surrogate to investigate immune responses to coronavirus infection.