{"doi":"10.4049/jimmunol.210.supp.241.02","title":"Ineffective polarization characterizes CD4 T cell responses to persistent <i>Borrelia burgdorferi</i> infection","abstract":"Abstract Borrelia burgdorferi (Bb), the spirochetal agent of Lyme disease, evades immune clearance in infected mice and humans, suggesting ongoing immune suppression. Here we explored the functionality of Bb-induced CD4 T cell responses in infected mice, which are considered Th1 polarized. Surprisingly, in vitro restimulation of CD4 T cells from mice infected for 12 days failed to induce secretion of the hallmark Th1 cytokine IFNg. Consistent with that data, flow cytometry and RNAseq of CD4 T cells from lymph nodes (LNs) of Bb-infected mice at 6, 10, 14, and 21 days post infection (dpi) showed a transient Th1 and Th17 polarization that peaked at 10 dpi before declining, confirmed also by RT-PCR. While Th1 and Th17 gene expression profiles returned to baseline by 14 dpi, increased frequencies of CXCR4+ CXCR5+ PD-1hi ICOS+ BCL6+ T follicular helper (Tfh) cells emerged at that time, concomitant with germinal center induction. The lack of CD4 T cell effector polarization was noted also in the skin, an effector site after Bb infection, as well as in antigen-specific T cells, which were identified using a new MHCII tetramer to the Bb surface antigen arthritis related protein (Arp). Together, our results indicate a failure to sustain effector CD4 T cell polarization after Bb infection, identifying CD4 T cells as a potential target of Bb-mediated immune suppression. This work was supported by grants from the Global Lyme Alliance, the Stephen &amp; Alexander Cohen Foundation, NIH R01AI157007 (NB) and T32 AI060555 (EMH). This work was supported by grants from the Global Lyme Alliance, the Stephen &amp; Alexander Cohen Foundation, NIH R01AI157007 (NB) and T32 AI060555 (EMH).","journal":"The Journal of Immunology","year":2023,"id":410192,"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":0.9613,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1190312,"name":"Inglis Tucker","orcid":null,"position":1,"is_corresponding":false},{"id":1088183,"name":"Kimberly J. Olsen","orcid":null,"position":2,"is_corresponding":false},{"id":568702,"name":"Priya S. Shah","orcid":"0000-0001-7518-2839","position":3,"is_corresponding":false},{"id":280803,"name":"Nicole Baumgarth","orcid":"0000-0002-2891-4483","position":4,"is_corresponding":false},{"id":939709,"name":"Elizabeth M. Hammond","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:21:31.144858Z","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":[]}