Results Healthy individuals andpatients with cystic fibrosis had robust antigen-specific memory CD4 + T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although they did express the chemokine receptor CCR6 that would direct migration to damaged epithelial surfaces. Furthermore, IL-22 production was evident in the lungs of CF patients colonised with PA. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 and Th1 cells, but the patient group had significantly fewer Th17 cells in peripheral blood. Conclusions MemoryTh22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with CF, with IL-22 secretion being demonstrated in the CF lung. These Th22 cells do not express tissue specificity for gut or skin sites and we thus hypothesise may have a role in respiratory defense. Along with Th17 cells, they may play an important role in the pathogenesis of pulmonary infection with this microbe in patients with cystic fibrosis.