Differential requirements of T cell subsets for CD40 costimulation in immunity to Blastomyces dermatitidis.
Cell-mediated immunity and production of type 1 cytokines are the main defenses against pathogenic fungi. Ligation of CD40 by CD40L on T cells is critical for the induction of these immune responses in vivo. We explored the role of CD40/CD40L interactions in vaccine immunity to Blastomyces dermatitidis by immunizing CD40(-/-) and CD40L(-/-) 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(-/-) and CD40L(-/-) 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.
Wüthrich
Marcel
M
Department of Pediatrics, University Hospital and Clinics, University of Wisconsin Medical School, 600 Highland Avenue, Madison, WI 53792, USA. mwuethri@wisc.edu
Fisette
Phil L
PL
Filutowicz
Hanna I
HI
Klein
Bruce S
BS
D000818:Animals; D017951:Antigen Presentation; D001758:Blastomyces / Q000502:physiology*; D001759:Blastomycosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism*; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D016764:Cell Polarity; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D014611:Vaccination
D019013:CD40 Antigens; D023201:CD40 Ligand