Specific activated T cells regulate IL-12 production by human monocytes stimulated with Cryptococcus neoformans.
IL-12 production mediated by a T cell-independent and/or T cell-dependent pathway was investigated in human monocytes responding to Cryptococcus neoformans. The data of this study showed that: 1) appreciable levels of IL-12 were observed when freshly isolated monocytes were exposed to acapsular C. neoformans or Candida albicans and secretion occurred within 24-48 h of incubation; 2) monocytes alone were poor producers of IL-12 when stimulated with encapsulated C. neoformans; 3) the presence of specific anti-glucuronoxylomannan mAb favored IL-12 secretion and Fc cross-linking could play a role; 4) monocytes were able to secrete consistent levels of IL-12 when cultured with activated T cells responding to C. neoformans; 5) the maximum secretion of IL-12 was observed at 5-7 days of culture and was strongly regulated by the presence of endogenous IFN-gamma; and 6) the interaction between CD40 on monocytes and CD40 ligand on activated T lymphocytes responding to C. neoformans played a critical role in IL-12 secretion. These data highlight the mechanisms of IL-12 production by human monocytes exposed to C. neoformans, indicating a possible biphasic secretion of IL-12, dependent on the direct effect of fungal insult, and characterized by consistent secretion of IL-12 that is dependent on the interaction of CD40 with the CD40 ligand expressed on activated T cells responding to C. neoformans.
Retini
C
C
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Casadevall
A
A
Pietrella
D
D
Monari
C
C
Palazzetti
B
B
Vecchiarelli
A
A
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000946:Antigens, Fungal; D019013:CD40 Antigens / Q000378:metabolism; D002176:Candida albicans / Q000276:immunology; D003455:Cryptococcus neoformans / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology*; D011134:Polysaccharides / Q000276:immunology; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology*