Endogenous mouse mammary tumor viruses influence the development of thymic αβ NKT cells and innate CD8+ T cells (111.26)

Abstract

Abstract Mounting evidence has demonstrated the presence of a population of thymic CD8+ T cells that share phenotypic and functional similarity to “innate-like” or “memory-like” T cells. Innate CD8+ T cells have increased expression of CD44, CD122, and Eomesodermin (Eomes), as well as the capacity to rapidly produce interferon (IFN)-γ upon stimulation. In addition to several gene-deficient models, including KLF2-, Itk-, and Id3-deficient mice, innate CD8+ T cells have also been documented in naïve BALB/c mice. The development of such cells is dependent on the production of interleukin (IL)-4 from an expanded population of αβ or γδ NKT cells expressing the transcription factor promyelocytic leukemia zinc finger (PLZF). Interestingly, this innate phenotype among CD8+ T cells is lost in congenic BALB/c mice lacking all endogenous mouse mammary tumor proviruses (BALB/Mtv-null). In the absence of endogenous Mtv proviruses, the expression of CD44, CD122, CXCR3, and Eomes, as well as the production of IFN-γ, was greatly reduced among thymic CD8+ T cells. The loss of this innate CD8+ T cell population in BALB/Mtv-null mice correlated with a reduction in PLZF+, IL-4 secreting αβ NKT cells within the thymus compared to wild type BALB/c. Our findings suggest a potential Mtv-mediated role in modulation of thymic αβ NKT cell development that subsequently influences the generation of innate CD8+ T cells.