Generation of IL-3-Secreting CD4⁺ T Cells by Microbial Challenge at Skin and Mucosal Barriers

During Ag priming, naive CD4⁺ T cells differentiate into subsets with distinct patterns of cytokine expression that dictate to a major extent their functional roles in immune responses. We identified a subset of CD4⁺ T cells defined by secretion of IL-3 that was induced by Ag stimulation under conditions different from those associated with previously defined functional subsets. Using mouse models of bacterial and viral infections, we showed that IL-3-secreting CD4⁺ T cells were generated by infection at the skin and mucosa but not by infections introduced directly into the blood. Most IL-3-producing T cells coexpressed GM-CSF and other cytokines that define multifunctionality. Generation of IL-3-secreting T cells in vitro was dependent on IL-1 family cytokines and was inhibited by cytokines that induce canonical Th1 or Th2 cells. Our results identify IL-3-secreting CD4⁺ T cells as a potential functional subset that arises during priming of naive T cells in specific tissue locations.