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In this study, we analysed the cellular response of hepatic lymph node cells and CD4<jats:sup>+<\/jats:sup> T cells in terms of proliferative response, efficiency of antigen presentation and cytokine production, to <jats:italic>F. hepatica<\/jats:italic>-derived molecules, at early and late stages of the infection. Thirty-one sheep were allocated into five groups and were slaughtered at 16 dpi and 23 wpi. In order to analyse antigen-specific response, the following <jats:italic>F. hepatica<\/jats:italic> recombinant molecules were used: rFhCL1, rFhCL2, rFhCL3, rFhCB1, rFhCB2, rFhCB3, rFhStf-1, rFhStf-2, rFhStf-3 and rFhKT1. A cell proliferation assay using hepatic lymph node cells and an antigen presentation cell assay using CD4<jats:sup>+<\/jats:sup> T cells were performed. At 16 dpi, all molecules but rFhStf-2 and rFhKT1 elicited a significant cell proliferative response on hepatic lymph node cells of infected animals. At both early and late stage of the infection, antigen presentation of rFhCB3 and rFhCL2 resulted in higher stimulation index of CD4<jats:sup>+<\/jats:sup> T cells which was IL-2 mediated, although no statistically significant when compared to uninfected animals. Significant cytokine production (IL-4, IL-10 and IFN-\u03b3) was conditioned by the antigen-specific cell stimulation. No CD4<jats:sup>+<\/jats:sup> T cell exhaustion was detected in infected sheep at the chronic stage of the infection. This study addressed antigen-specific response to <jats:italic>F. hepatica<\/jats:italic>-derived molecules that are involved in key aspects of the parasite survival within the host.<\/jats:p>","DOI":"10.1186\/s13567-021-00963-5","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T17:05:16Z","timestamp":1625245516000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antigen-specific response of CD4+ T cells and hepatic lymph node cells to Fasciola hepatica-derived molecules at the early and late stage of the infection in sheep"],"prefix":"10.1186","volume":"52","author":[{"given":"Ra\u00fal","family":"P\u00e9rez-Caballero","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8438-3077","authenticated-orcid":false,"given":"F. 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The procedure was approved by the University of Cordoba Bioethics Committee (code no. 1118).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"99"}}