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

Mice immunized with peritoneal exudate cells (PEC; used as antigen-presenti ng cells [APC]) that are pulsed ex vivo with cryptococcal capsular polyysac charide, a glucuronoxylomannan (GXM), exhibit increased survival times and delayed-type hypersensitivity reactions when they are infected with Cryptoc occus neoformans. These responses are GXM specific. The present study revea led that GXM-APC immunization enhanced development of anticryptococcal type -1 cytokine responses (interleukin-2 [IL-2] and gamma interferon) in mice i nfected with C. neoformans. The enhancement was not GXM specific, because i mmunization with GXM-APC and immunization with APC alone had similar effect s. GXM-APC (or APC) immunization caused small increases in the expression o f type-2 cytokines (IL-4 and IL-5), but the increases were not always stati stically 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 i neffective. 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 popu lation was not attributed to their production of IL-12 because GXM-APC prep ared 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 r evealed that early induction of IL-12 secretion was not responsible for the immunomodulatory response elicited by GXM-APC. These data, considered toge ther with previously reported data, reveal that the protective activity of GXM-APC immunization involves both antigen-specific and nonspecific activit ies of GXM-APC.