CpG oligodeoxynucleotides can reverse Th2-associated allergic airway responses and alter the B7.1/B7.2 expression in a murine model of asthma

被引:109
作者
Serebrisky, D
Teper, AA
Huang, CK
Lee, SY
Zhang, TF
Schofield, BH
Kattan, M
Sampson, HA
Li, XM
机构
[1] Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA
[2] Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA
关键词
D O I
10.4049/jimmunol.165.10.5906
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CpG oligodeoxynucleotides (CpG-ODN) administered during Ag sensitization or before Ag challenge can inhibit allergic pulmonary inflammation and airway hyperreactivity in murine models of asthma, In this study, we investigated whether CpG-ODN ran reverse an ongoing allergic pulmonary reaction in a mouse model of asthma, AKR mice were sensitized with conalbumin followed by two intratracheal challenges at weekly intervals. CpG-ODN was administered 24 h after the first Ag challenge. CpG-ODN administration reduced Ag-specific IgE levels, bronchoalveolar lavage fluid eosinophils, mucus production, and airway hyperreactivity. We found that postchallenge CpG-ODN treatment significantly increased IFN-gamma concentrations and decreased IL-13, IL-4, and IL-5 concentrations in bronchoalveolar lavage fluids and spleen cell culture supernatants. Postchallenge CpG-ODN treatment also increased B7.1 mRNA expression and decreased B7.2 mRNA expression in lung tissues. These results suggest that CpG-ODN may have potential for treatment of allergic asthma by suppressing Th2 responses during IgE-dependent allergic airway reactions, The down-regulation of Th2 responses by CPG-ODN may be associated with regulation of the costimulatory factors B7.1 and B7.2.
引用
收藏
页码:5906 / 5912
页数:7
相关论文
共 42 条
[31]   The role of lymphocytes in allergic disease [J].
Romagnani, S .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2000, 105 (03) :399-408
[32]   QUANTITATIVE STRUCTURAL-ANALYSIS OF PERIPHERAL AIRWAYS AND ARTERIES IN SUDDEN FATAL ASTHMA [J].
SAETTA, M ;
DISTEFANO, A ;
ROSINA, C ;
THIENE, G ;
FABBRI, LM .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1991, 143 (01) :138-143
[33]  
SEREBRISKY D, 2000, AM J RESP CRIT CARE, V161, pA591
[34]   Regulation of T-helper type 2 cell and airway eosinophilia by transmucosal coadministration of antigen and oligodeoxynucleotides containing CpG motifs [J].
Shirota, H ;
Sano, K ;
Kikuchi, T ;
Tamura, G ;
Shirato, K .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2000, 22 (02) :176-182
[35]   An investigation of the temporal induction of cytokine mRNAs in LPS-challenged thioglycollate-elicited murine peritoneal macrophages using the reverse transcription polymerase chain reaction [J].
Simpson, AECM ;
Tomkins, PT ;
Cooper, KL .
INFLAMMATION RESEARCH, 1997, 46 (02) :65-71
[36]  
Sparwasser T, 1998, EUR J IMMUNOL, V28, P2045, DOI 10.1002/(SICI)1521-4141(199806)28:06<2045::AID-IMMU2045>3.0.CO
[37]  
2-8
[38]   Type I interferon-mediated stimulation of T cells by CgG DNA [J].
Sun, SQ ;
Zhang, XH ;
Tough, DF ;
Sprent, J .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (12) :2335-2342
[39]  
Sur S, 1999, J IMMUNOL, V162, P6284
[40]   Immunologic basis of antigen-induced airway hyperresponsiveness [J].
Wills-Karp, M .
ANNUAL REVIEW OF IMMUNOLOGY, 1999, 17 :255-281