title: Regulation of cytokine expression in mice immunized with cryptococcal polysaccharide, a glucuronoxylomannan (GXM), associated with peritoneal antigen-presenting cells (APC): requirements for GXM, APC activation, and interleukin-12.
abstract: Mice immunized with peritoneal exudate cells (PEC; used as antigen-presenting cells [APC]) that are pulsed ex vivo with cryptococcal capsular polysaccharide, a glucuronoxylomannan (GXM), exhibit increased survival times and delayed-type hypersensitivity reactions when they are infected with Cryptococcus neoformans. These responses are GXM specific. The present study revealed that GXM-APC immunization enhanced development of anticryptococcal type-1 cytokine responses (interleukin-2 [IL-2] and gamma interferon) in mice infected with C. neoformans. The enhancement was not GXM specific, because immunization with GXM-APC and immunization with APC alone had similar effects. GXM-APC (or APC) immunization caused small increases in the expression of type-2 cytokines (IL-4 and IL-5), but the increases were not always statistically significant. IL-10 levels were not regulated by immunization with GXM-APC or APC. GXM-APC prepared with PEC harvested from mice injected with complete Freund's adjuvant (CFA) enhanced type-1 cytokine responses, while GXM-APC prepared with PEC induced with incomplete Freund's adjuvant were ineffective. The CFA-induced PEC had an activated phenotype characterized by increased numbers of F4/80(+) cells that expressed CD40, B7-1, and B7-2 on their membranes. The immunomodulatory activity of the CFA-induced APC population was not attributed to their production of IL-12 because GXM-APC prepared with peritoneal cells harvested from IL-12 knockout mice or their wild-type counterparts were equally effective in augmenting the type-1 response. Blocking of IL-12 in the recipients of GXM-APC early after APC infusion revealed that early induction of IL-12 secretion was not responsible for the immunomodulatory response elicited by GXM-APC. These data, considered together with previously reported data, reveal that the protective activity of GXM-APC immunization involves both antigen-specific and nonspecific activities of GXM-APC.
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190, USA. becky-blackstock@ouhsc.edu
authors.forename: R
authors.initials: R
authors.lastname: Blackstock
authors.forename: N
authors.initials: N
authors.lastname: McElwee
authors.forename: E
authors.initials: E
authors.lastname: Neller
authors.forename: J
authors.initials: J
authors.lastname: Shaddix-White
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D003455:Cryptococcus neoformans / Q000276:immunology*; D005260:Female; D005657:Fungal Vaccines / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011134:Polysaccharides / Q000276:immunology*
chemical_list: D005657:Fungal Vaccines; D011134:Polysaccharides; D018664:Interleukin-12; C027478:glucuronoxylomannan; D007371:Interferon-gamma