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We explored the role of CD40\/CD40L interactions in vaccine immunity to Blastomyces dermatitidis by immunizing CD40\u2212\/\u2212 and CD40L\u2212\/\u2212 mice and analyzing their resistance to reinfection in a murine pulmonary model. In the absence of CD40 or CD40L, CD4+ cells failed to get primed or produce type 1 cytokine and impaired the generation of CD8+ T1 cells. The CD8+ T cell defect was not due to regulatory T cells or impaired APC maturation or Ag presentation to T cells. If CD4+ cells were first eliminated, vaccination of CD40\u2212\/\u2212 and CD40L\u2212\/\u2212 mice restored priming of CD8+ cells, type 1 cytokine production, and resistance. Hence, CD4+ and CD8+ cells differ sharply in their requirement for CD40\/CD40L interaction during the generation of antifungal immunity. Despite the plasticity of T cell subsets in vaccine immunity, in absence of CD40\/CD40L interaction, CD4+ cells may impede the priming of CD8+ cells at the cost of host survival against a lethal infectious disease.<\/jats:p>","DOI":"10.4049\/jimmunol.176.9.5538","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:31:36Z","timestamp":1398029496000},"page":"5538-5547","source":"Crossref","is-referenced-by-count":13,"title":["Differential Requirements of T Cell Subsets for CD40 Costimulation in Immunity to\n                    <i>Blastomyces dermatitidis<\/i>"],"prefix":"10.1093","volume":"176","author":[{"given":"Marcel","family":"Wu\u0308thrich","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phil L","family":"Fisette","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna I","family":"Filutowicz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce S","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"},{"name":"Department of Internal Medicine, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"},{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"},{"name":"Comprehensive Cancer Center, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2006,5,1]]},"reference":[{"key":"2026020211410781200_R1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/978-1-4615-3306-1_11","volume-title":"Blastomycosis","year":"1992"},{"key":"2026020211410781200_R2","first-page":"398","volume-title":"Infect. 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