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Interferons (IFNs) are a family of proteins that are generated in response to viral infection and induce an antiviral response in many cell types. The COVID-19 pandemic revealed that patients with inborn errors of type-I IFN immunity were more prone to severe infections, but also found that many patients with severe COVID-19 had anti-IFN autoantibodies that led to acquired defects in type-I IFN immunity. These findings revealed the previously unappreciated finding that central immune tolerance to IFN is essential to immune health. Further evidence has also highlighted the importance of IFN within the thymus and its impact on T-cell development. This review will highlight what is known of IFN's role in T-cell development, T-cell central tolerance, and the impact of IFN on the thymus. [ABSTRACT FROM AUTHOR]

• Intestinal IEL are a heterogeneous lymphocyte population. • In adult animals, the majority of CD8αα IEL precursors are self-reactive thymocytes that undergo agonist selection. • Alternative, and likely functionally distinct, precursors exist. The intestinal epithelium is the outermost cellular layer that separates the body from the gut lumen. The integrity of this protective mucosal barrier is crucial and maintained by specialized cells—intraepithelial lymphocytes (IEL). Much research has been conducted on these cells and our overall understanding of them is increasing rapidly. In this review we focus on the TCRαβ+ subset of CD8αα IEL. We discuss recent studies that shed light on the development, ontogeny, maintenance, and functional characteristics of CD8αα IEL, and highlight yet unanswered questions for future studies. [ABSTRACT FROM AUTHOR]

T cells can sometimes acquire properties of a memory cell without encountering foreign antigen. Miller et al. now show that development of such 'memory phenotype' (MP) CD8+ T cells starts with recognition of self-ligands in the thymus, and finishes in peripheral tissues. These cells respond rapidly during infection, and infiltrate tumors, where they express high amounts of PD-1. [ABSTRACT FROM AUTHOR]