GM-CSF+ Tc17 cells are required to bolster vaccine immunity against lethal fungal pneumonia without causing overt pathology

Abstract

GM-CSF co-expressing T17 cells instigate pathologic inflammation during autoimmune disorders, but their function in immunity to infections is unclear. Here, we demonstrate the role of GM-CSF⁺Tc17 cells for vaccine immunity against lethal fungal pneumonia and the cytokine requirements for their induction and memory homeostasis. Vaccine-induced GM-CSF⁺ Tc17 cells are necessary to bolster pulmonary fungal immunity without inflating pathology. Although GM-CSF expressing Tc17 cells preferentially elevate during the memory phase, their phenotypic attributes strongly suggest they are more like Tc17 cells than IFNγ-producing Tc1 cells. IL-1 and IL-23, but not GM-CSF, are necessary to elicit GM-CSF⁺ Tc17 cells following vaccination. IL-23 is dispensable for memory Tc17 and GM-CSF⁺ Tc17 cell maintenance, but recall responses of effector or memory Tc17 cells in the lung require it. Our study reveals the beneficial, nonpathological role of GM-CSF⁺ Tc17 cells during fungal vaccine immunity.

Keywords: CP: Immunology; GM-CSF; GM-CSF(+) Tc17 cells; IL-1; IL-17A; IL-23; fungal; immunity; pathology; vaccine.