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In this study, we used a fate-mapping mouse model to characterize CX3CR1+CD4+ T cells during both acute Nippostrongylus brasiliensis and chronic Schistosoma mansoni murine models of helminth infections, revealing CX3CR1+CD4+ T cells to be an activated tissue-homing subset with varying capacity for cytokine production. Tracking these cells over time revealed that maintenance of CX3CR1 itself along with a TH2 phenotype conferred a survival advantage in the inflamed tissue. Single-cell RNA sequencing analysis of fate-mapped CX3CR1+CD4+ T cells from both the peripheral tissue and the spleen revealed a considerable level of diversity and identified a distinct population of BCL6+TCF-1+PD1+CD4+ T cells in the spleen during helminth infections. Conditional deletion of BCL6 in CX3CR1+ cells resulted in fewer CX3CR1+CD4+ T cells during infection, indicating a role in sustaining CD4+ T cell responses to helminth infections. Overall, our studies revealed the behavior and heterogeneity of CX3CR1+CD4+ T cells during type 2 inflammation in helminth infections and identified BCL6 to be important in their maintenance.<\/jats:p>","DOI":"10.4049\/jimmunol.2300451","type":"journal-article","created":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T14:07:34Z","timestamp":1704463654000},"page":"632-644","source":"Crossref","is-referenced-by-count":7,"title":["Recruitment and Maintenance of CX3CR1+CD4+ T Cells during Helminth Infection"],"prefix":"10.1093","volume":"212","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7889-7776","authenticated-orcid":false,"given":"Denis G","family":"Loredan","sequence":"first","affiliation":[{"name":"Department of Microbiology, New York University Grossman School of Medicine , New York, NY"},{"name":"Vilcek Institute of Graduate Biomedical Sciences, New York University Grossman School of Medicine , New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph C","family":"Devlin","sequence":"additional","affiliation":[{"name":"Department of Microbiology, New York University Grossman School of Medicine , New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9328-3817","authenticated-orcid":false,"given":"Kamal M","family":"Khanna","sequence":"additional","affiliation":[{"name":"Department of Microbiology, New York University Grossman School of Medicine , New York, NY"},{"name":"Perlmutter Cancer Center, New York University Grossman School of Medicine , New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6211-3292","authenticated-orcid":false,"given":"P\u2019ng","family":"Loke","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,1,5]]},"reference":[{"key":"2025020405450059500_r1","doi-asserted-by":"crossref","first-page":"e2865","DOI":"10.1371\/journal.pntd.0002865","article-title":"The global burden of disease study 2010: interpretation and implications for the neglected tropical diseases","volume":"8","author":"Hotez","year":"2014","journal-title":"PLoS Negl. 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