Antibody to Cryptococcus neoformans capsular glucuronoxylomannan promotes expression of interleukin-12Rbeta2 subunit on human T cells in vitro through effects mediated by antigen-presenting cells.
The results reported herein show that T cells responding to encapsulated Cryptococcus neoformans cells had reduced expression of interleukin-12 receptor beta2 (IL-12Rbeta2) in comparison to those responding to non-encapsulated cells. This suggested that encapsulation with glucuronoxylomannan (GXM), the principal constituent of the C. neoformans polysaccharide antiphagocytic capsule, inhibited expression of the IL-12Rbeta2 subunit on T cells responding to cryptococcal antigens. Addition of GXM-binding monoclonal antibody (mAb) overcame this effect by promoting IL-12Rbeta2 expression and by decreasing IL-1R expression on T cells. This effect may be a consequence of mAb-induced changes on antigen-presenting cells (APC) that are closely related to increased phagocytosis. Blocking of phagocytosis with monoiodacetic acid (MIA) precluded up-regulation of B7 expression on APC and was associated with diminished IL-12Rbeta2 expression on T cells. The observed effects on T cells were interpreted as a consequence of increased APC function due to enhanced phagocytosis. These findings suggest a mechanism by which specific antibody can promote the polarization of the cellular immune response towards a Th1-like response and thus contribute to an enhanced cellular immune response against C. neoformans.
Vecchiarelli
Anna
A
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy. vecchiar@unipg.it
Pietrella
Donatella
D
Bistoni
Francesco
F
Kozel
Thomas R
TR
Casadevall
Arturo
A
D000908:Antibodies, Fungal / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000946:Antigens, Fungal / Q000276:immunology; D002478:Cells, Cultured; D003455:Cryptococcus neoformans / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D010587:Phagocytosis / Q000276:immunology; D011134:Polysaccharides / Q000276:immunology*; D018123:Receptors, Interleukin / Q000378:metabolism*; D053707:Receptors, Interleukin-12; D013601:T-Lymphocytes / Q000276:immunology*
D000908:Antibodies, Fungal; D000946:Antigens, Fungal; C508439:IL12RB2 protein, human; D011134:Polysaccharides; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; C027478:glucuronoxylomannan