ArticlePLoS pathogens2019
Thymic expression of IL-4 and IL-15 after systemic inflammatory or infectious Th1 disease processes induce the acquisition of "innate" characteristics during CD8+ T cell development.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Association of IL18 genetic polymorphisms with Chagas disease in Latin American populations.PLoS neglected tropical diseases · 2019Pooled it
- Innate T-αβ lymphocytes as new immunological components of anti-tumoral "off-target" effects of the tyrosine kinase inhibitor dasatinib.Scientific reports · 2020Trial
- Virtual memory CD8⁺ T cells in aging: heterogeneity, bystander protection, inflammatory potential, and inhibitory regulation.Immunity & ageing : I & A · 2026Review
- Revisiting T cells: Innate actions and emerging links to innate memory response.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Bystander CD8Frontiers in immunology · 2025Article
- Article
- Roles of Virtual Memory T Cells in Diseases.Immune network · 2023Review
- Virtual Memory CD8Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2022Review
- Systemic sterile induced-co-expression of IL-12 and IL-18 drive IFN-γ-dependent activation of microglia and recruitment of MHC-II-expressing inflammatory monocytes into the brain.International immunopharmacology · 2022Article
- Safety levels of systemic IL-12 induced by cDNA expression as a cancer therapeutic.Immunotherapy · 2022Article
- Human CD4 T Cells From Thymus and Cord Blood Are Convertible Into CD8 T Cells by IL-4.Frontiers in immunology · 2022Article
- Thymus, undernutrition, and infection: Approaching cellular and molecular interactions.Frontiers in nutrition · 2022Review
- Exploring the immunomodulatory role of virtual memory CD8Frontiers in immunology · 2022Article
- Signals for antigen-independent differentiation of memory CD8Cellular and molecular life sciences : CMLS · 2021Review
- CD138 expression is a molecular signature but not a developmental requirement for RORγt+ NKT17 cells.JCI insight · 2021Article
- Host-parasite dynamics in Chagas disease from systemic to hyper-local scales.Parasite immunology · 2021Review
- Hiding in Plain Sight: Virtually Unrecognizable Memory Phenotype CD8International journal of molecular sciences · 2020Review
- The Thymus in Chagas Disease: Molecular Interactions Involved in Abnormal T-Cell Migration and Differentiation.Frontiers in immunology · 2020Review
- Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Innate CD8+ T cells express a memory-like phenotype and demonstrate a strong cytotoxic capacity that is critical during the early phase of the host response to certain bacterial and viral infections. These cells arise in the thymus and depend on IL-4 and IL-15 for their development. Even though innate CD8+ T cells exist in the thymus of WT mice in low numbers, they are highly enriched in KO mice that lack certain kinases, leading to an increase in IL-4 production by thymic NKT cells. Our work describes that in C57BL/6 WT mice undergoing a Th1 biased infectious disease, the thymus experiences an enrichment of single positive CD8 (SP8) thymocytes that share all the established phenotypical and functional characteristics of innate CD8+ T cells. Moreover, through in vivo experiments, we demonstrate a significant increase in survival and a lower parasitemia in mice adoptively transferred with SP8 thymocytes from OT I-T. cruzi-infected mice, demonstrating that innate CD8+ thymocytes are able to protect against a lethal T. cruzi infection in an Ag-independent manner. Interestingly, we obtained similar results when using thymocytes from systemic IL-12 + IL-18-treated mice. This data indicates that cytokines triggered during the acute stage of a Th1 infectious process induce thymic production of IL-4 along with IL-15 expression resulting in an adequate niche for development of innate CD8+ T cells as early as the double positive (DP) stage. Our data demonstrate that the thymus can sense systemic inflammatory situations and alter its conventional CD8 developmental pathway when a rapid innate immune response is required to control different types of pathogens.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.