MHC class II expression in human basophils: induction and lack of functional significance

PLoS One. 2013 Dec 9;8(12):e81777. doi: 10.1371/journal.pone.0081777. eCollection 2013.

Abstract

The antigen-presenting abilities of basophils and their role in initiating a Th2 phenotype is a topic of current controversy. We aimed to determine whether human basophils can be induced to express MHC Class II and act as antigen presenting cells for T cell stimulation. Isolated human basophils were exposed to a panel of cytokines and TLR-ligands and assessed for MHC Class II expression. MHC Class II was expressed in up to 17% of isolated basophils following incubation with a combination of IL-3, IFN-γ and GM-CSF for 72 hours. Costimulatory molecules (CD80 and CD86) were expressed at very low levels after stimulation. Gene expression analysis of MHC Class II-positive basophils confirmed up-regulation of HLA-DR, HLA-DM, CD74 and Cathepsin S. However, MHC Class II expressing basophils were incapable of inducing antigen-specific T cell activation or proliferation. This is the first report of significant cytokine-induced MHC Class II up-regulation, at both RNA and protein level, in isolated human basophils. By testing stimulation with relevant T cell epitope peptide as well as whole antigen, the failure of MHC Class II expressing basophils to induce T cell response was shown not to be solely due to inefficient antigen uptake and/or processing.

MeSH terms

  • Antigen Presentation
  • Antigens, Differentiation, B-Lymphocyte / genetics*
  • Antigens, Differentiation, B-Lymphocyte / immunology
  • B7-1 Antigen / genetics
  • B7-1 Antigen / immunology
  • B7-2 Antigen / genetics
  • B7-2 Antigen / immunology
  • Basophils / cytology*
  • Basophils / drug effects
  • Basophils / immunology
  • Cathepsins / genetics
  • Cathepsins / immunology
  • Cells, Cultured
  • Coculture Techniques
  • Gene Expression
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • HLA-D Antigens / genetics*
  • HLA-D Antigens / immunology
  • HLA-DR Antigens / genetics*
  • HLA-DR Antigens / immunology
  • Histocompatibility Antigens Class II / genetics*
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-3 / pharmacology
  • Th2 Cells / cytology*
  • Th2 Cells / drug effects
  • Th2 Cells / immunology

Substances

  • Antigens, Differentiation, B-Lymphocyte
  • B7-1 Antigen
  • B7-2 Antigen
  • HLA-D Antigens
  • HLA-DM antigens
  • HLA-DR Antigens
  • Histocompatibility Antigens Class II
  • Interleukin-3
  • invariant chain
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Cathepsins
  • cathepsin S

Grants and funding

This work was supported by Ilhan Food Allergy Foundation, the National Health and Medical Research Council of Australia and The Alfred Research Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.