Abstract
Streptococcus pneumoniae is the most common etiology of bacterial pneumonia, one of the leading causes of death in children and the elderly worldwide. During non-lethal infections with S. pneumoniae, lymphocytes accumulate in the lungs and protect against reinfection with serotype-mismatched strains. Cluster of differentiation CD4(+) resident memory T (T(RM)) cells are known to be crucial for this protection, but the diversity of lung CD4(+) T(RM) cells has yet to be fully delineated. We aimed to identify unique subsets and their contributions to lung immunity. After recovery from pneumococcal infections, we identified a distinct subset of CD4(+) T cells defined by the phenotype CD11a(hi)CD69(+)GL7(+) in mouse lungs. Phenotypic analyses for markers of lymphocyte memory and residence demonstrated that GL7(+) T cells are a subset of CD4(+) T(RM) cells. Functional studies revealed that unlike GL7(-) T(RM) subsets that were mostly (RAR-related Orphan Receptor gamma T) RORγT(+), GL7(+) T(RM) cells exhibited higher levels of (T-box expressed in T cells) T-bet and Gata-3, corresponding with increased synthesis of interferon-γ, interleukin-13, and interleukin-5, inherent to both T helper 1 (T(H)1) and T(H)2 functions. Thus, we propose that these cells provide novel contributions during pneumococcal pneumonia, serving as important determinants of lung immunity.