DNA from Mycobacterium bovis bacillus Calmette-Guérin (MY-1) inhibits immunoglobulin E production by human lymphocytes

Am J Respir Crit Care Med. 1999 Dec;160(6):2056-61. doi: 10.1164/ajrccm.160.6.9903008.

Abstract

A DNA fraction purified from Mycobacterium bovis bacillus Calmette-Guérin (BCG) and designated MY-1 induced interferon (IFN)-gamma production by human peripheral blood mononuclear cells (PBMC). IFN-gamma is well known as a downregulator of IgE production. In this study we investigated whether MY-1 regulates IgE production by human PBMC in vitro. MY-1 inhibited IgE production in PBMC taken from normal donors and stimulated with interleukin (IL)-4 plus monoclonal anti-CD40 antibody, without affecting production of IgA. MY-1 enhanced production of IFN-gamma and IL-12 by PBMC. Inhibition by MY-1 of IgE production was mediated by both IFN-gamma and IL-12, since the MY-1-induced suppression was blocked by the addition of monoclonal anti-IFN-gamma antibody, monoclonal anti-IL-12 antibody or a monoclonal antibody (mAb) directed at the IL-12 receptor. MY-1 inhibited the induction of epsilon germ-line transcript by IL-4. Additionally, MY-1 inhibited spontaneous in vitro production of IgE by PBMC from atopic donors in the absence of IL-4 plus anti-CD40 mAb. These results suggest that exposure to MY-1 may be a novel strategy for the treatment of IgE-related allergic disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • CD40 Antigens / immunology
  • Cells, Cultured
  • DNA, Bacterial / pharmacology*
  • Humans
  • Hypersensitivity, Immediate / immunology
  • Immunoglobulin E / biosynthesis*
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / biosynthesis
  • Interleukin-4 / pharmacology
  • Lymphocytes / immunology*
  • Mycobacterium bovis / genetics*

Substances

  • Antibodies, Monoclonal
  • CD40 Antigens
  • DNA, Bacterial
  • Interleukin-12
  • Interleukin-4
  • Immunoglobulin E
  • Interferon-gamma