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


CONCLUSIONS
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.
Watanabe
Tomohiro
T
Department of Clinical Bio-regulatory Science, Kyoto University Graduate School of Medicine, Shogoin Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan.
Katsukura
Hiroaki
H
Shirai
Yasuhiko
Y
Yamori
Masashi
M
Chiba
Tsutomu
T
Kita
Toru
T
Wakatsuki
Yoshio
Y
D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D002478:Cells, Cultured; D017637:Clonal Deletion; D053222:Fas Ligand Protein; D005512:Food Hypersensitivity / Q000276:immunology; D019672:Genes, T-Cell Receptor; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000235:genetics / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology*
D000941:Antigens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin