Antibody to Cryptococcus neoformans capsular glucuronoxylomannan promotes expression of interleukin-12Rβ2 subunit on human T cells in vitro through effects mediated by antigen-presenting cells

Abstract

The results reported herein show that T cells responding to encapsulated Cryptococcus neoformans cells had reduced expression of interleukin-12 receptor β2 (IL-12Rβ2) 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-12Rβ2 subunit on T cells responding to cryptococcal antigens. Addition of GXM-binding monoclonal antibody (mAb) overcame this effect by promoting IL-12Rβ2 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-12Rβ2 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.