Abstract
Tissue-resident memory T cells (T-RM cells) are crucial mediators of adaptive immunity in nonlymphoid tissues. However, the functional heterogeneity and pathogenic roles of CD4(+) T-RM cells that reside within chronic inflammatory lesions remain unknown. We found that CD69(hi)CD103(lo) CD4(+) T-RM cells produced effector cytokines and promoted the inflammation and fibrotic responses induced by chronic exposure to Aspergillus fumigatus. Simultaneously, immunosuppressive CD69(hi)CD103(hi)Foxp3(+) CD4(+) regulatory T cells were induced and constrained the ability of pathogenic CD103(lo) T-RM cells to cause fibrosis. Thus, lung tissue-resident CD4(+) T cells play crucial roles in the pathology of chronic lung inflammation, and CD103 expression defines pathogenic effector and immunosuppressive tissue-resident cell subpopulations in the inflamed lung.