Invariant NKT Cells Act as an Adjuvant to Enhance Th2 Inflammatory Response in an OVA-Induced Mouse Model of Asthma

被引:41
作者
Nie, Hanxiang [1 ]
Yang, Qiaoyu [1 ]
Zhang, Guqin [2 ]
Wang, Ailing [3 ]
He, Qing [1 ]
Liu, Min [1 ]
Li, Ping [2 ]
Yang, Jiong [2 ]
Huang, Yi [1 ]
Ding, Xuhong [1 ]
Yu, Hongying [1 ]
Hu, Suping [1 ]
机构
[1] Wuhan Univ, Renmin Hosp, Dept Resp Med, Wuhan 430072, Peoples R China
[2] Wuhan Univ, Zhongnan Hosp, Dept Resp Med, Wuhan 430072, Peoples R China
[3] Wuhan Univ, HOPE Sch Nursing, Wuhan 430072, Peoples R China
基金
中国国家自然科学基金;
关键词
KILLER T-CELLS; AIRWAY INFLAMMATION; DENDRITIC CELLS; IN-VIVO; ACTIVATION; CD4(+); HYPERREACTIVITY; INFECTION; IMMUNITY; INNATE;
D O I
10.1371/journal.pone.0119901
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background Invariant natural killer T cells (iNKT cells) are a unique subset of T lymphocytes and are considered to play an important role in the development of allergic bronchial asthma. Recently, iNKT cells were shown to play an immunoregulatory role in CD4(+) and CD8(+) T cell-mediated adaptive immune response. Allergen-specific Th2 inflammatory responses are an important part of the adaptive immune response in asthma. However, the regulatory functions of the Th2 inflammatory response in asthma have not been studied in detail. Method In this study, we have investigated the regulatory functions of iNKT cells on the Th2 inflammatory response in an ovalbumin (OVA)-induced murine model of asthma. Results Our results demonstrate that alpha-Galactosylceramide (alpha-GalCer) administration activated iNKT cells but could not induce the Th2 inflammatory response in wild-type (WT) mice. In the OVA-induced asthma model, alpha-GalCer administration and adoptive transfer of iNKT cells significantly augmented the Th2 inflammatory responses, including elevated inflammatory cell infiltration in the lung and bronchoalveolar lavage fluid (BALF); increased levels of IL-4, IL-5, and IL-13 in the BALF and splenocyte culture supernatant; and increased serum levels of OVA-specific IgE and IgG1. In addition, the Th2 inflammatory response was reduced, but not completely abrogated in CD1d(-/)-mice immunized and challenged with OVA, compared with WT mice. Conclusion These results suggest that iNKT cells may serve as an adjuvant to enhance Th2 inflammatory response in an OVA-induced murine model of asthma.
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页数:16
相关论文
共 26 条
[1]   CD4+ invariant T-cell-receptor plus natural killer T cells in bronchial asthma. [J].
Akbari, O ;
Faul, JL ;
Hoyte, EG ;
Berry, GJ ;
Wahlström, J ;
Kronenberg, M ;
DeKruyff, RH ;
Umetsu, DT .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (11) :1117-1129
[2]   Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity [J].
Akbari, O ;
Stock, P ;
Meyer, E ;
Kronenberg, M ;
Sidobre, S ;
Nakayama, T ;
Taniguchi, M ;
Grusby, MJ ;
DeKruyff, RH ;
Umetsu, DT .
NATURE MEDICINE, 2003, 9 (05) :582-588
[3]   Natural Killer T Cells: An Unconventional T-Cell Subset with Diverse Effector and Regulatory Functions [J].
Balato, Anna ;
Unutmaz, Derya ;
Gaspari, Anthony A. .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2009, 129 (07) :1628-1642
[4]   The biology of NKT cells [J].
Bendelac, Albert ;
Savage, Paul B. ;
Teyton, Luc .
ANNUAL REVIEW OF IMMUNOLOGY, 2007, 25 :297-336
[5]   Mechanism of CD1d-restricted natural killer T cell activation during microbial infection [J].
Brigl, M ;
Bry, L ;
Kent, SC ;
Gumperz, JE ;
Brenner, MB .
NATURE IMMUNOLOGY, 2003, 4 (12) :1230-1237
[6]   A critical role for natural killer T cells in immunosurveillance of methylcholanthrene-induced sarcomas [J].
Crowe, NY ;
Smyth, MJ ;
Godfrey, DI .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (01) :119-127
[7]   Selective bystander proliferation of memory CD4+ and CD8+ T cells upon NK T or T cell activation [J].
Eberl, G ;
Brawand, P ;
MacDonald, HR .
JOURNAL OF IMMUNOLOGY, 2000, 165 (08) :4305-4311
[8]   Recognition of Lyso-Phospholipids by Human Natural Killer T Lymphocytes [J].
Fox, Lisa M. ;
Cox, Daryl G. ;
Lockridge, Jennifer L. ;
Wang, Xiaohua ;
Chen, Xiuxu ;
Scharf, Louise ;
Trott, David L. ;
Ndonye, Rachel M. ;
Veerapen, Natacha ;
Besra, Gurdyal S. ;
Howell, Amy R. ;
Cook, Mark E. ;
Adams, Erin J. ;
Hildebrand, William H. ;
Gumperz, Jenny E. .
PLOS BIOLOGY, 2009, 7 (10)
[9]   Activation of natural killer T cells by α-galactosylceramide rapidly induces the full maturation of dendritic cells in vivo and thereby acts as an adjuvant for combined CD4 and CD8 T cell immunity to a coadministered protein [J].
Fujii, S ;
Shimizu, K ;
Smith, C ;
Bonifaz, L ;
Steinman, RM .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (02) :267-279
[10]   Murine CD1d-restricted T cell recognition of cellular lipids [J].
Gumperz, JE ;
Roy, C ;
Makowska, A ;
Lum, D ;
Sugita, M ;
Podrebarac, T ;
Koezuka, Y ;
Porcelli, SA ;
Cardell, S ;
Brenner, MB ;
Behar, SM .
IMMUNITY, 2000, 12 (02) :211-221