A Dominant CD4+ T-Cell Response to Helicobacter pylori Reduces Risk for Gastric Disease in Humans

被引:34
作者
Chen, Li [1 ]
Li, Bin [1 ]
Yang, Wu-Chen [2 ]
He, Jia-Lin [2 ]
Li, Ning-Yi [1 ]
Hu, Jian [2 ]
He, Ya-Fei [2 ]
Yu, Shu [3 ]
Zhao, Zhuo [1 ]
Luo, Ping [1 ]
Zhang, Jin-Yong [1 ]
Li, Hai-Bo [1 ]
Zeng, Ming [4 ]
Lu, Dong-Shui [1 ]
Li, Bo-Sheng [1 ]
Guo, Hong [2 ]
Yang, Shi-Ming [2 ]
Guo, Gang [1 ]
Mao, Xu-Hu [1 ]
Chen, Weisan [5 ]
Wu, Chao [1 ]
Zou, Quan-Ming [1 ]
机构
[1] Third Mil Med Univ, Coll Med Lab Sci, Dept Clin Microbiol & Immunol, Xinqiao Hosp, Chongqing 400038, Peoples R China
[2] Third Mil Med Univ, Dept Gastroenterol, Xinqiao Hosp, Chongqing 400038, Peoples R China
[3] Peoples Liberat Army, Inst Logist Engn, Dept Outpatients, Chongqing, Peoples R China
[4] Natl Inst Food & Drug Control, Beijing, Peoples R China
[5] La Trobe Univ, Sch Mol Sci, Cell Lab T, Bundoora, Vic 3086, Australia
基金
中国国家自然科学基金;
关键词
Stomach; Bacterial Infection; Immunization; Disease Prevention; PEPTIC-ULCER; CROSS-REACTIVITY; ANTIGEN; INFECTION; HPAA; IDENTIFICATION; IMMUNIZATION; ANTRUM; MICE; LOCALIZATION;
D O I
10.1053/j.gastro.2012.12.002
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
BACKGROUND & AIMS: Immunodominance is an important feature of antiviral, antitumor, and antibacterial cellular immune responses, but it is not well demonstrated in the immune responses against Helicobacter pylori. Antigen-specific CD4(+) T cells protect mice against infection with H pylori. We investigated the immunodominant CD4(+) T-cell response to neuraminyllactose-binding hemagglutinin (HpaA), which is a conserved, H pylori-specific colonization factor that is being investigated as an antigen for vaccination strategies. METHODS: HpaA-specific CD4(+) T cells were expanded with autologous peripheral blood mononuclear cells that had been incubated with recombinant HpaA and characterized using overlapping synthetic peptides. We compared the percentage of CD4(+) T cells with specificity for HpaA(88-100), restricted to HLA-DRB1*1501, among 59 H pylori-infected subjects with different gastric diseases. RESULTS: We identified and characterized several immunodominant CD4(+) T-cell epitopes derived from HpaA. The immunodominant CD4(+) T-cell responses specific to HpaA(88-100) were observed in most H pylori-infected individuals who expressed HLA-DRB1*1501 and were significantly more abundant in patients with less severe diseases (P < .05). CONCLUSIONS: The HLA-DRB1*1501-restricted immunodominant CD4(+) T-cell response to HpaA(88-100) is associated with reduced risk of severe gastric diseases. Further study of these and other immunodominant CD4(+) T-cell responses to H pylori will provide insight into mechanisms of protective immunity and aid in vaccine design.
引用
收藏
页码:591 / 600
页数:10
相关论文
共 35 条
[1]   Protection against Helicobacter pylori infection following immunization is IL-12-dependent and mediated by Th1 cells [J].
Akhiani, AA ;
Pappo, J ;
Kabok, Z ;
Schön, K ;
Gao, W ;
Franzén, LE ;
Lycke, N .
JOURNAL OF IMMUNOLOGY, 2002, 169 (12) :6977-6984
[2]   Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori [J].
Alm, RA ;
Ling, LSL ;
Moir, DT ;
King, BL ;
Brown, ED ;
Doig, PC ;
Smith, DR ;
Noonan, B ;
Guild, BC ;
deJonge, BL ;
Carmel, G ;
Tummino, PJ ;
Caruso, A ;
Uria-Nickelsen, M ;
Mills, DM ;
Ives, C ;
Gibson, R ;
Merberg, D ;
Mills, SD ;
Jiang, Q ;
Taylor, DE ;
Vovis, GF ;
Trost, TJ .
NATURE, 1999, 397 (6715) :176-180
[3]  
Ardito Matthew, 2011, Immunome Res, V7
[4]   Lymphocytes in the human gastric mucosa during Helicobacter pylori have a T helper cell 1 phenotype [J].
Bamford, KB ;
Fan, XJ ;
Crowe, SE ;
Leary, JF ;
Gourley, WK ;
Luthra, GK ;
Brooks, EG ;
Graham, DY ;
Reyes, VE ;
Ernst, PB .
GASTROENTEROLOGY, 1998, 114 (03) :482-492
[5]  
Blom K, 2001, FEMS IMMUNOL MED MIC, V30, P173
[6]   Extensive homology between the major immunodominant mitochondrial antigen in primary biliary cirrhosis and Helicobacter pylori does not lead to immunological cross-reactivity [J].
Bogdanos, DP ;
Baum, H ;
Gunsar, F ;
Arioli, D ;
Polymeros, D ;
Ma, Y ;
Burroughs, AK ;
Vergani, D .
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 2004, 39 (10) :981-987
[7]   HpaA is essential for Helicobacter pylori colonization in mice [J].
Carlsohn, E ;
Nyström, J ;
Bölin, I ;
Nilsson, CL ;
Svennerholm, AM .
INFECTION AND IMMUNITY, 2006, 74 (02) :920-926
[8]   Untitled [J].
Chen, QJ ;
Wahlgren, M ;
Waters, AP .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 2004, 134 (01) :1-1
[9]   Higher Frequency of T-Cell Response to M. tuberculosis Latency Antigen Rv2628 at the Site of Active Tuberculosis Disease than in Peripheral Blood [J].
Chiacchio, Teresa ;
Petruccioli, Elisa ;
Vanini, Valentina ;
Butera, Ornella ;
Cuzzi, Gilda ;
Petrone, Linda ;
Matteucci, Giuseppe ;
Lauria, Francesco Nicola ;
Franken, Kees L. M. C. ;
Girardi, Enrico ;
Ottenhoff, Tom H. M. ;
Goletti, Delia .
PLOS ONE, 2011, 6 (11)
[10]   Pathogenesis of Helicobacter pylori Infection [J].
Costa, Ana C. ;
Figueiredo, Ceu ;
Touati, Eliette .
HELICOBACTER, 2009, 14 :15-20