Evaluating the in vivo Th2 priming potential among common allergens

被引:19
作者
Camberis, Mali [1 ]
Prout, Melanie [1 ]
Tang, Shiau-Choot [1 ]
Forbes-Blom, Elizabeth [1 ]
Robinson, Marcus [1 ]
Kyle, Ryan [1 ]
Belkaid, Yasmine [2 ]
Paul, William [3 ]
Le Gros, Graham [1 ]
机构
[1] Malaghan Inst Med Res, Wellington 6242, New Zealand
[2] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA
[3] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA
关键词
Allergenicity; In vivo Th2 immunoassay; CD4 T cell; Interleukin-4; House dust mite; eGFP-reporter; HOUSE-DUST MITE; T-CELLS; CROSS-REACTIVITY; RESPONSES; ANTIGEN; RECEPTOR; MICE; SENSITIZATION; EOSINOPHILIA; INFECTION;
D O I
10.1016/j.jim.2013.05.004
中图分类号
Q5 [生物化学];
学科分类号
070307 [化学生物学];
摘要
Exposure to allergens, both man-made and from our environment is increasingly associated with the development of significant human health issues such as allergy and asthma. Allergen induced production of the cytokine interleukin (IL-)4 by Th2 cells is central to the pathogenesis of allergic disease (Gavett et al., 1994). The development of the G4 mouse, that expresses green fluorescent protein (GFP) as a surrogate for IL-4 protein expression has made it possible to directly track the immune cells that produce IL-4. By combining a reliable intradermal immunisation technique with the transgenic G4 mouse we have been able to develop a novel & unique in vivo primary Th2 immune response model (PTh2). When allergens relevant to human disease are evaluated using the PTh2 assay a dose dependent hierarchy of allergenicity is revealed with environmental allergens (cockroach, house dust mite) the most potent and food allergens being the least. In addition, the PTh2 assay is extremely sensitive to the immunoregulatory effects of Mycobacterial extracts and immunosuppressive drugs on primary Th2 cell development. Taken together, this assay provides a standardised method for the identification of the structural and functional properties of proteins relevant to allergenicity, and is a powerful screening tool for novel lead compounds that are effective at inhibiting the primary Th2 response in allergic diseases. (c) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:62 / 72
页数:11
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