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Control of Cryptosporidium requires CD4+ T cells, but how protective CD4+ T cell responses are generated is poorly understood. Here, Cryptosporidium parasites that express MHCII-restricted model antigens were generated to understand the basis for CD4+ T cell priming and effector function. These studies revealed that parasite-specific CD4+ T cells are primed in the draining mesenteric lymph node but differentiate into Th1 cells in the gut to provide local parasite control. Although type 1 conventional dendritic cells (cDC1s) were dispensable for CD4+ T cell priming, they were required for CD4+ T cell gut homing and were a source of IL-12 at the site of infection that promoted local production of IFN-\u03b3. Thus, cDC1s have distinct roles in shaping CD4+ T cell responses to an enteric infection: first, to promote gut homing from the mesLN, and second, to drive effector responses in the intestine.<\/jats:p>","DOI":"10.1084\/jem.20232067","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T02:21:14Z","timestamp":1715048474000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Intestinal cDC1s provide cues required for CD4+ T cell\u2013mediated resistance to\n                    <i>Cryptosporidium<\/i>"],"prefix":"10.1084","volume":"221","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2286-4646","authenticated-orcid":true,"given":"Ian S.","family":"Cohn","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00b30xv10","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Veterinary Medicine, University of Pennsylvania 1 Department of Pathobiology, , 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