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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

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.