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The inoculation of healthy adults with vaccinia virus presents an opportunity to study these events intensively. Between days 11 and 14 postinoculation, there was a peak of proliferating CCR5<jats:sup>+<\/jats:sup>CD38<jats:sup>+++<\/jats:sup>CD4<jats:sup>+<\/jats:sup>effector cells which contained the cytotoxic granule marker T-cell intracellular antigen 1 and included gamma interferon (IFN-\u03b3)-producing vaccinia virus-specific CD4<jats:sup>+<\/jats:sup>T cells. The majority of these initial vaccinia virus-specific CD4<jats:sup>+<\/jats:sup>T cells were CD127<jats:sup>+<\/jats:sup>and produced interleukin-2 (IL-2) but not CTLA-4 in response to restimulation in vitro. Between days 14 and 21, there was a switch from IFN-\u03b3 and IL-2 coexpression to IL-2 production only, coinciding with a resting phenotype and an increased in vitro proliferation response. The early CCR5<jats:sup>+<\/jats:sup>CD38<jats:sup>+++<\/jats:sup>vaccinia virus-specific CD4<jats:sup>+<\/jats:sup>T cells were similar to our previous observations of human immunodeficiency virus (HIV)-specific CD4<jats:sup>+<\/jats:sup>T cells in primary HIV type 1 (HIV-1) infection, but the vaccinia virus-specific cells expressed much more CD127 and IL-2 than we previously found in their HIV-specific counterparts. The current study provides important information on the differentiation of IL-2<jats:sup>+<\/jats:sup>vaccinia virus-specific memory cells, allowing further study of antiviral effector CD4<jats:sup>+<\/jats:sup>T cells in healthy adults and their dysfunction in HIV-1 infection.<\/jats:p>","DOI":"10.1128\/jvi.02670-05","type":"journal-article","created":{"date-parts":[[2006,9,27]],"date-time":"2006-09-27T22:19:39Z","timestamp":1159395579000},"page":"10151-10161","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":43,"title":["CD127<sup>+<\/sup>CCR5<sup>+<\/sup>CD38<sup>+++<\/sup>CD4<sup>+<\/sup>Th1 Effector Cells Are an Early Component of the Primary Immune Response to Vaccinia Virus and Precede Development of Interleukin-2<sup>+<\/sup>Memory CD4<sup>+<\/sup>T Cells"],"prefix":"10.1128","volume":"80","author":[{"given":"John J.","family":"Zaunders","sequence":"first","affiliation":[{"name":"Centre for Immunology, St. 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Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"De Rose","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Kent","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Viral Immunology Laboratory, Tissue Typing Department, Australian Red Cross Blood Service, Sydney, NSW 2000, Australia"},{"name":"Transfusion Medicine and Immunogenetics Research Unit, Faculty of Medicine, University of Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David 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