{"doi":"10.33915/etd.12856","title":"The characterization of IL-27 production and its impact on T cell antigen-specificity and diversity in a neonatal BCG vaccination model","abstract":"Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb), and it has plagued humans for most of recorded history. Despite strong efforts to prevent and treat TB, it remains the leading cause of death due to a pathogen and is most prevalent in certain regions of Asia and Africa. Currently, the only approved vaccine to prevent TB is the live-attenuated Bacillus Calmette-Guérin (BCG) vaccine. Most countries have a universal BCG vaccination policy, but the vaccine ultimately fails to be protective. The BCG vaccine is most effective in children and protects against disseminated TB, but protection wanes 10-15 years after vaccination causing adults to be unprotected against pulmonary TB. There are many hypotheses that attempt to explain the failure of the BCG vaccine, including the time of life it is administered. The BCG vaccine is administered during the neonatal period when the immune system is skewed towards Th2 responses. Our lab has specifically demonstrated that the immunosuppressive cytokine interleukin (IL)-27 is elevated during this time. We have also shown that BCG vaccination further elevates already heightened levels of IL-27, and that in the absence of IL-27 signaling there is improved control of Mtb following BCG vaccination. This suggests IL-27 interferes with protective immune responses induced by the BCG vaccine and that neutralization of IL-27 may improve vaccine responses. However, it is first important to fully understand the kinetics and phenotype of IL-27 producers following BCG vaccination. To explore this, we used IL-27p28eGFP mice in combination with our neonatal BCG vaccination model. We observed via flow cytometry that IL-27 continuously increases throughout the first five weeks post-vaccination in both the spleen and lung. Most IL-27 producers were CD11b+ and F4/80+ with a significant increase in MHC class II expression following BCG vaccination. Single cell RNA-sequencing and ATAC-sequencing analysis further confirmed that IL-27 producers have improved antigen processing and presentation capabilities following BCG vaccination. Overall, we learned that IL-27 producers following BCG vaccination are a heterogenous group of myeloid cells with diverse phenotypes. We then wanted to understand how IL-27 produced by these cells impacts the specificity and diversity of T cells following BCG vaccination. We previously demonstrated that IL-27 interferes with phagosome maturation, so we hypothesized that IL-27 reduces the diversity of antigens processed and presented via MHC class II, leading to a reduction in the abundance and diversity of antigen-specific T cells. To explore this, we vaccinated wildtype (WT) and IL-27RαKO mice","journal":"The Research Repository @ WVU (West Virginia University)","year":2025,"id":567072,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":307749,"name":"Ashley M. Divens","orcid":"0000-0003-4793-4129","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:56:40.491968Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}