Differential requirements of T cell subsets for CD40 costimulation in immunity to Blastomyces dermatitidis. Journal of immunology (Baltimore, Md. : 1950) [J Immunol] Journal article

Title	Differential requirements of T cell subsets for CD40 costimulation in immunity to Blastomyces dermatitidis.
Author(s)	Wüthrich M, Fisette PL, Filutowicz HI, Klein BS
Institution	Department of Pediatrics, University Hospital and Clinics, University of Wisconsin Medical School, 600 Highland Avenue, Madison, WI 53792, USA. mwuethri@wisc.edu
Source	J Immunol 2006 May 1; 176(9):5538-47.
MeSH	Animals Antigen Presentation Antigens, CD40 Blastomyces Blastomycosis Bone Marrow CD4-Positive T-Lymphocytes CD40 Ligand CD8-Positive T-Lymphocytes Cell Differentiation Cell Polarity Cells, Cultured Dendritic Cells Mice Mice, Inbred C57BL Mice, Knockout Research Support, U.S. Gov't, P.H.S. T-Lymphocyte Subsets Vaccination
Abstract	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.
Language	eng
Pub Type(s)	Journal Article
PubMed ID	16622023

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