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Artículo

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

Baez, Natalia SoledadIcon ; Cerban, Fabio MarceloIcon ; Savid Frontera, ConstanzaIcon ; Hodge, Deborah L.; Tosello Boari, JimenaIcon ; Acosta Rodriguez, Eva VirginiaIcon ; Almada, LauraIcon ; Gruppi, AdrianaIcon ; Viano, María EstefaníaIcon ; Young, Howard A.; Rodriguez Galan, Maria CeciliaIcon
Fecha de publicación: 11/2019
Editorial: Public Library of Science
Revista: Plos Pathogens
ISSN: 1553-7366
e-ISSN: 1553-7374
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Otras Ciencias de la Salud

Resumen

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.
Palabras clave: IL-4 , IL-15 , INFECTIOUS TH1 PROCESSES , INNATES CD8+T CELLS
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/128582
URL: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007456
DOI: https://doi.org/10.1371/journal.ppat.1007456
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Articulos(CIBICI)
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Citación
Baez, Natalia Soledad; Cerban, Fabio Marcelo; Savid Frontera, Constanza; Hodge, Deborah L.; Tosello Boari, Jimena; et al.; 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; Public Library of Science; Plos Pathogens; 15; 1; 11-2019; 1-32
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