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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]

Clonal selection is central to immune function, but it is complemented by ‘receptor selection’, which regulates the immune repertoire not by cell death or proliferation but through the control of antigen receptor gene recombination. Inappropriate receptors, such as those that are autoreactive, underexpressed, or that fail to promote positive selection of thymocytes or B cells, stimulate secondary V-to-J recombinations that destroy and replace receptor genes. These processes play a central role in lymphocyte repertoire development. Recent work on the role of receptor selection in B and T cells has uncovered evidence for and against antigen-induced editing in thymocytes. Many studies suggest that editing plays a central role in B and T lymphocyte repertoire development. Important recent evidence has been uncovered addressing the role of tolerance-induced editing in thymocytes. [Copyright &y& Elsevier]

A prominent population of innate CD8+ T cells develops in the thymus of several gene-deficient mouse strains, including Itk, KLF2, CBP and Id3. These cells have the phenotype and function of memory CD8+ T cells, without previous exposure to antigen. Surprisingly, the cytokine IL-4 plays a key role in their development. As this developmental mechanism was discovered, it came to light that innate CD8+ T cells exist also in normal mice and in humans. In this review, we discuss how these cells develop, compare and contrast them to other CD8 memory cells, and discuss their potential physiological relevance. [Copyright &y& Elsevier]