Lyon De Ana, CarolinaShenoy, Anukul TBarker, Kimberly AArafa, Emad IEtesami, Neelou SKorkmaz, Filiz TSoucy, Alicia MBreen, Michael PMartin, Ian M CTilton, Brian RDevarajan, PriyadharshiniCrossland, Nicholas APihl, Riley M FGoltry, Wesley NBelkina, Anna CJones, Matthew RQuinton, Lee JMizgerd, Joseph P2025-06-112025-06-112023-09-14Lyon De Ana C, Shenoy AT, Barker KA, Arafa EI, Etesami NS, Korkmaz FT, Soucy AM, Breen MP, Martin IMC, Tilton BR, Devarajan P, Crossland NA, Pihl RMF, Goltry WN, Belkina AC, Jones MR, Quinton LJ, Mizgerd JP. GL7 ligand expression defines a novel subset of CD4+ TRM cells in lungs recovered from pneumococcus. Mucosal Immunol. 2023 Oct;16(5):699-710. doi: 10.1016/j.mucimm.2023.07.004. Epub 2023 Sep 14. PMID: 37604254; PMCID: PMC10591822.1935-345610.1016/j.mucimm.2023.07.00437604254S1933-0219(23)00056-9https://hdl.handle.net/20.500.14038/54510Streptococcus 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) cells are known to be crucial for this protection, but the diversity of lung CD4 T 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 CD11aCD69GL7 in mouse lungs. Phenotypic analyses for markers of lymphocyte memory and residence demonstrated that GL7 T cells are a subset of CD4 T cells. Functional studies revealed that unlike GL7 T subsets that were mostly (RAR-related Orphan Receptor gamma T) RORγT, GL7 T 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 (T1) and T2 functions. Thus, we propose that these cells provide novel contributions during pneumococcal pneumonia, serving as important determinants of lung immunity.en© 2023 The Author(s). Published by Elsevier Inc. on behalf of Society for Mucosal Immunology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).http://creativecommons.org/licenses/by-nc-nd/4.0/Journal Article