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 N; CERBÁN F; SAVID FRONTERA C; HODGE DL; ACOSTA RODRIGUEZ EV; YOUNG HA; RODRIGUEZ GALAN MC

PLOS PATHOGENS

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2019

1553-7366

Innate CD8+ T cells express a memory-like phenotype and demonstrate a strong cytotoxiccapacity that is critical during the early phase of the host response to certain bacterial andviral 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-4production by thymic NKT cells. Our work describes that in C57BL/6 WT mice undergoing aTh1 biased infectious disease, the thymus experiences an enrichment of single positiveCD8 (SP8) thymocytes that share all the established phenotypical and functional characteristicsof innate CD8+ T cells. Moreover, through in vivo experiments, we demonstrate a significantincrease in survival and a lower parasitemia in mice adoptively transferred with SP8thymocytes from OT I?T. cruzi-infected mice, demonstrating that innate CD8+ thymocytesare 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 Th1infectious process induce thymic production of IL-4 along with IL-15 expression resulting inan 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 situationsand alter its conventional CD8 developmental pathway when a rapid innate immuneresponse is required to control different types of pathogens.