GL7 ligand expression defines a novel subset of CD4(+) T(RM) cells in lungs recovered from pneumococcus

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.