{"doi":"10.4049/jimmunol.1500247","title":"Limited Internodal Migration of T Follicular Helper Cells after Peripheral Infection with Herpes Simplex Virus-1","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>The ability of CD4 T cells to give rise to specialized T follicular helper cells (TFH) critical to initiating appropriate Ab responses is regulated by environmental cues in lymphoid tissues draining the site of infection. In this study, we used a skin infection with HSV-1 characterized by the successive involvement of interconnected but distinct lymph nodes (LNs), to investigate the anatomical diversification of virus-specific CD4 T cell responses and the migratory capacity of TFH or their precursors. Whereas Th1 effector CD4 T cells expressing peripheral-targeting migration molecules readily migrated from primary to secondary reactive LNs, Bcl6+ CXCR5+ PD1hi TFH were largely retained at the site of initial activation with little spillover into the downstream LNs involved at later stages of infection. Consistent with this, TFH maintained high-level surface expression of CD69, indicative of impaired migratory capacity. Notably, the biased generation and retention of TFH in primary LNs correlated with a preferential generation of germinal centers at this site. Our results highlight a limited anatomical diversification of TFH responses and germinal center reactions that were imprinted within the first few cell divisions during TFH differentiation in LNs draining the site of initial infection.</jats:p>","journal":"The Journal of Immunology","year":2015,"id":604744,"datarank":0.10913442510500684,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.005162348021015038,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.005162348021015038,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1551713,"name":"Christopher M Harpur","orcid":null,"position":1,"is_corresponding":false},{"id":1551714,"name":"Bethany L Macleod","orcid":null,"position":2,"is_corresponding":false},{"id":1551715,"name":"Paul G Whitney","orcid":null,"position":3,"is_corresponding":false},{"id":904234,"name":"Thomas Gebhardt","orcid":"0000-0002-3768-9468","position":4,"is_corresponding":false},{"id":1551716,"name":"Andrew G Brooks","orcid":null,"position":5,"is_corresponding":false},{"id":1551711,"name":"Sanda Stankovic","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Limited Internodal Migration of T Follicular Helper Cells after Peripheral Infection with Herpes Simplex Virus-1","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>The ability of CD4 T cells to give rise to specialized T follicular helper cells (TFH) critical to initiating appropriate Ab responses is regulated by environmental cues in lymphoid tissues draining the site of infection. In this study, we used a skin infection with HSV-1 characterized by the successive involvement of interconnected but distinct lymph nodes (LNs), to investigate the anatomical diversification of virus-specific CD4 T cell responses and the migratory capacity of TFH or their precursors. Whereas Th1 effector CD4 T cells expressing peripheral-targeting migration molecules readily migrated from primary to secondary reactive LNs, Bcl6+ CXCR5+ PD1hi TFH were largely retained at the site of initial activation with little spillover into the downstream LNs involved at later stages of infection. Consistent with this, TFH maintained high-level surface expression of CD69, indicative of impaired migratory capacity. Notably, the biased generation and retention of TFH in primary LNs correlated with a preferential generation of germinal centers at this site. Our results highlight a limited anatomical diversification of TFH responses and germinal center reactions that were imprinted within the first few cell divisions during TFH differentiation in LNs draining the site of initial infection.</jats:p>","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26453747","pmcid":null,"openalex_id":"https://openalex.org/W2411658258","authors":[],"funders":[],"total_grants":0,"fwci":0.0,"citation_percentile":0.16721873,"influential_citations":0,"citation_trend":[{"year":2025,"count":1}],"oa_status":"closed","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://academic.oup.com/jimmunol/article-pdf/195/10/4892/62248857/1500247.pdf","host_type":"publisher"},{"url":"https://doi.org/10.4049/jimmunol.1500247","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26453747","host_type":"repository"}],"fields_of_study":["T-cell and B-cell Immunology","Immune Response and Inflammation","Immunotherapy and Immune Responses"],"mesh_terms":["CD69 Antigens","Animals","Antigens, Differentiation, T-Lymphocyte","Cell Differentiation","Cell Movement","DNA-Binding Proteins","Herpes Simplex","Mice, Transgenic","Antigens, CD","Herpesvirus 1, Human","Th1 Cells","Germinal Center","Lectins, C-Type","Mice","Proto-Oncogene Proteins c-bcl-6","Receptors, CXCR5"],"keywords":["Germinal center","BCL6","CXCR5","Biology","Immunology","Effector","Lymph","Virus","Follicular phase","Herpes simplex virus","Virology","Cell biology","B cell","Antibody","Genetics","Medicine","Pathology"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T00:50:24.484867Z","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":[]}