GL7 ligand expression defines a novel subset of CD4+ TRM cells in lungs recovered from pneumococcus

• DOI: 10.1016/j.mucimm.2023.07.004
• Publication Date: 2023-09-15T05:14:48Z
• Authors: Carolina Lyon De Ana; Anukul T. Shenoy; Kimberly A. Barker; Emad I. Arafa; Neelou S. Etesami; Filiz T. Korkmaz; Alicia M. Soucy; Michael P. Breen; Ian M.C. Martin; Brian R. Tilton; Priyadharshini De...; Nicholas A. Cross...; Riley M.F. Pihl; Wesley N. Goltry; Anna C. Belkina; Matthew R. Jones; Lee J. Quinton; Joseph P. Mizgerd
• Keywords: CD4-Positive T-Lymphocytes; Mice; Streptococcus pneumoniae; T-Lymphocytes; Animals; Humans; Child; Ligands; Immunologic Memory; Lung; Article; Aged

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 (TRM) cells are known to be crucial for this protection, but the diversity of lung CD4+ TRM 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 CD11ahiCD69+GL7+ in mouse lungs. Phenotypic analyses for markers of lymphocyte memory and residence demonstrated that GL7+ T cells are a subset of CD4+ TRM cells. Functional studies revealed that unlike GL7- TRM subsets that were mostly (RAR-related Orphan Receptor gamma T) RORγT+, GL7+ TRM 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 (TH1) and TH2 functions. Thus, we propose that these cells provide novel contributions during pneumococcal pneumonia, serving as important determinants of lung immunity.