{"doi":"10.1093/jimmun/vkaf283.129","title":"Unraveling Helminth-Specific T Cells: Insights from Gene Editing in Strongyloides ratti 2176","abstract":"Abstract Description CD4+ helper 2 (TH2) cells are crucial for protective Type 2 immunity against parasitic helminths, but the importance of antigen-specificity in this context remains a controversial topic. This study, generated, characterized and employed a novel CRISPR-targeted Strongyloides ratti mutant to interrogate the functional role of helminth-specific CD4 T cells. Termed Atilla, this parasite line expresses two copies of the immunodominant CD4+ T cell epitope 2W1S, fused with FLAG and HA peptides from the astacin-like metalloendopeptidase gene locus. Infected C57BL/6 mice with Atilla show significant expansion of 2W1S tetramer positive CD4+ T cells in the lung, spleen, mesenteric lymph nodes, and peritoneal cavity. Peptide re-stimulation experiments show increased type 2 cytokine release compared to controls, and repeated inoculation of mice with Attila progressively expands a memory-like 2W1S+CD62L-CD44+CD4+ population that co-expresses GATA3, T1/ST2, and CXCR6. Adoptive transfer of enriched 2W1S+CD62L-CD44+CD4+ T cells into naïve C57BL/6 mice lacking alpha-beta and gamma-delta T cells was sufficient to confer protection against subsequent parasite challenge. These findings support the hypothesis that antigen-specific CD4+ T cells have a role in anti-helminth immunity, and ongoing studies seek to test whether they are functionally superior to “bystander” non-antigen specific TH2 cells. Funding Sources NIH U01AI163062 NIH R01AI164715 NIH 1R21AI171740 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)","journal":"The Journal of Immunology","year":2025,"id":582551,"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":0.9552,"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":1494631,"name":"Olufemi Akinkuoutu","orcid":null,"position":1,"is_corresponding":false},{"id":264130,"name":"Annabel A. Ferguson","orcid":"0000-0002-9691-7184","position":2,"is_corresponding":false},{"id":361130,"name":"Hannah E. Dobson","orcid":"0000-0003-1246-880X","position":3,"is_corresponding":false},{"id":652796,"name":"Adriana Stephenson","orcid":null,"position":4,"is_corresponding":false},{"id":1173615,"name":"Ulrich Membe Femoe","orcid":"0000-0001-8715-152X","position":5,"is_corresponding":false},{"id":264125,"name":"Li‐Yin Hung","orcid":"0000-0001-7623-1946","position":6,"is_corresponding":false},{"id":1494632,"name":"Parvathi Annamalai","orcid":null,"position":7,"is_corresponding":false},{"id":300707,"name":"Juan M. Inclan-Rico","orcid":"0000-0003-1134-9139","position":8,"is_corresponding":false},{"id":473182,"name":"Heather L. Rossi","orcid":"0000-0003-1983-7997","position":9,"is_corresponding":false},{"id":264138,"name":"De’Broski R. Herbert","orcid":"0000-0002-2449-5365","position":10,"is_corresponding":false},{"id":1221804,"name":"Fungai Musaigwa","orcid":"0000-0003-0216-0385","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:58:55.657290Z","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":[]}