Helper CD4+ T cells for IgE response to a dietary antigen develop in the liver

J Allergy Clin Immunol. 2003 Jun;111(6):1375-85. doi: 10.1067/mai.2003.1466.

Abstract

Background: Although T-cell responses to food antigens are normally inhibited either by deletion, active suppression, or both of antigen-specific T cells, T helper cells for IgE response to a food antigen still develop by unknown mechanisms in a genetically susceptible host.

Objective: We determined the site at which those IgE helper T cells develop.

Methods: We administered ovalbumin (OVA) orally to DO11.10 mice and studied CD4+ T cells in Peyer's patches, the spleen, and the liver. Helper activity for IgE response was assessed by adoptively transferring those CD4+ T cells to naive BALB/c mice, followed by systemic immunization with OVA.

Results: OVA-specific CD4+ T cells were deleted by cell death in the liver and Peyer's patches of DO11.10 mice fed OVA. OVA-specific CD4+ T cells that survived apoptosis in the liver expressed Fas ligand and secreted IL-4, IL-10, and transforming growth factor beta(1). CD4+ T cells producing IFN-gamma were deleted in the liver by repeated feeding of OVA. On transfer of CD4+ T cells to naive mice and systemic immunization with OVA, a marked increase in OVA-specific IgE response developed only in the mice that received hepatic CD4+ T cells from OVA-fed mice, the effect of which was not observed in the recipients of hepatic CD4+ T cells deficient in IL-4. In addition, significant suppression of delayed-type hypersensitivity and IgG(1)/IgG(2a) responses to OVA was observed in the recipients of hepatic CD4+ T cells, and this suppression required Fas/Fas ligand interaction.

Conclusion: Together, these results suggested that a food antigen might negatively select helper T cells for IgE response to the antigen by preferential deletion of T(H)1 cells in the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adoptive Transfer
  • Animals
  • Antigens / administration & dosage
  • Antigens / immunology*
  • Cells, Cultured
  • Clonal Deletion
  • Fas Ligand Protein
  • Food Hypersensitivity / immunology
  • Genes, T-Cell Receptor
  • Hypersensitivity, Delayed / immunology
  • Immunoglobulin E / biosynthesis*
  • Interleukin-4 / genetics
  • Interleukin-4 / physiology
  • Liver / cytology
  • Liver / immunology*
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mice, Transgenic
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology*
  • Peyer's Patches / cytology
  • Peyer's Patches / immunology
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / transplantation
  • Th2 Cells / immunology*

Substances

  • Antigens
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • Interleukin-4
  • Immunoglobulin E
  • Ovalbumin