Interleukin-21 reduces Listeria monocytogenes secondary infection via CD8＋ effector memory T cells

Background: Purpose: Interleukin-21 （IL-21） is mainly produced from CD4＋ T cells and has broad impact on immune responses. IL-21 isoform is a splicing variant of IL-21 and is functionally similar to conventional IL-21. We established IL-21 isoform transgenic mice （IL-21isoTg）, which constitutively express IL-21 isoform specifically in T cells. IL-21isoTg possess high amount of CD8＋ T cells in normal physiological condition. The purpose of this study is to determine whether CD8＋ T cells in the IL-21isoTg work against intracellular bacteria infection.Methods: Wild type mice （WT） and IL-21isoTg are orally inoculated Listeria monocytogenes （L. monocytogenes） on day 0, and 15 days after primary infection. Bacterial load in each organs, and T cell responses are analyzed.Results: IL-21isoTg and WT had similar bacterial load after primary infection. On the other hand, after secondary infection, IL-21isoTg exhibited reduced bacterial load in some organs and showed higher levels of CD8＋ effector memory T （TEM） cells tnWT.Conclusion: IL-21-induced CD8＋ TEM cells might eventually reduce the bacterial load after secondary infection. To the best of our knowledge, this is the first study to show that IL-21 is a pivotal factor involved in eliminating intracellular bacteria, probably through CD8＋ TEM cells.