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

Immunology. 2002 Jun;106(2):267-72. doi: 10.1046/j.1365-2567.2002.01419.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Fungal / immunology*
  • Antigen-Presenting Cells / immunology*
  • Antigens, Fungal / immunology
  • Cells, Cultured
  • Cryptococcus neoformans / immunology*
  • Humans
  • Immunity, Cellular
  • Phagocytosis / immunology
  • Polysaccharides / immunology*
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-12
  • T-Lymphocytes / immunology*

Substances

  • Antibodies, Fungal
  • Antigens, Fungal
  • IL12RB2 protein, human
  • Polysaccharides
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • glucuronoxylomannan