CD4(+) T cells from food allergy model are resistant to TCR-dependent apoptotic induction.
BACKGROUND
CD4(+) T cell polarization plays a critical role in the pathogenesis of allergy. How to modulate the skewed CD4(+) T cell polarization is less clear. The specific immunotherapy (SIT) is the only specific remedy for the treatment of allergic diseases; the therapeutic effect is to be improved.


OBJECTIVE
This study aims to investigate the role of interleukin (IL)-18 in enhancing the therapeutic effect of SIT.


METHODS
A peanut allergy mouse model was developed and treated with SIT or/and IL-18. CD4(+) T cell apoptosis was assessed by flow cytometry. The expression of Fas ligand (FasL) was observed by quantitative real time RT-PCR and Western blotting. Interferon-γ in the culture medium was determined by enzyme-linked immunosorbent assay. The fasL gene promoter methylation in CD4(+) T cells was assessed by methylation specific PCR.


RESULTS
The results showed that lower levels of IL-18 were detected in allergic mice; administration of IL-18 significantly enhanced the therapeutic effect of SIT on suppressing the allergic inflammation in the mouse intestine. In the cell culture studies, IL-18 increased the TCR-dependent CD4(+) T cell apoptosis, the expression of FasL in CD4(+) T cells, the production of Interferon-γ and the demethylation of the FasL promoter in CD4(+) T cells.


CONCLUSIONS
Administration of IL-18 enhances the effect of SIT on suppressing allergic inflammation in the mouse intestine via enhancing the TCR-dependent CD4(+) T cell apoptosis.
State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
Weiyi
W
He
State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
Chengbin
C
Yang
State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
Lixin
L
Xia
Longgang Central Hospital, ENT Hospital, Shenzhen ENT Institute, Shenzhen, China.
Mei-Zhen
MZ
Zhao
State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
Rong-Ti
RT
Ge
State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
Haizheng
H
Huang
State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
Qiongmei
Q
Ji
State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China. Electronic address: pcy2356@szu.edu.cn.
Ping-Chang
PC
Yang
State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China. Electronic address: lzg195910@126.com.
Zhigang
Z
Liu
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017931:DNA Primers; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein / Q000097:blood; D005434:Flow Cytometry; D020382:Interleukin-18 / Q000097:blood; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D021183:Peanut Hypersensitivity / Q000276:immunology* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
D017931:DNA Primers; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D020382:Interleukin-18; D011948:Receptors, Antigen, T-Cell
Allergy; CD4 T cell; Fas ligand; Interleukin-18; T cell receptor