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

Authors

• Natalia S. Baez, Universidad Nacional de Córdoba
• Fabio Cerbán, Universidad Nacional de Córdoba
• Constanza Savid-Frontera, Universidad Nacional de Córdoba
• Deborah L. Hodge, National Cancer Institute at Frederick
• Jimena Tosello, Universidad Nacional de Córdoba
• Eva Acosta-Rodriguez, Universidad Nacional de Córdoba
• Laura Almada, Universidad Nacional de Córdoba
• Adriana Gruppi, Universidad Nacional de Córdoba
• Maria Estefania Viano, Universidad Nacional de Córdoba
• Howard A. Young, National Cancer Institute at FrederickFollow
• Maria Cecilia Rodriguez-Galan, Universidad Nacional de CórdobaFollow

Date of this Version

1-1-2019

Citation

Baez NS, Cerba´n F, Savid-Frontera C, Hodge DL, Tosello J, Acosta-Rodriguez E, et al. (2019) 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. PLoS Pathog 15(1): e1007456. https://doi.org/ 10.1371/journal.ppat.1007456

Comments

The work is made available under the Creative Commons CC0 public domain dedication.

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.