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在大鼠模型中,抗原特异性T细胞和B细胞反应的调节影响肺部不可分型流感嗜血杆菌的细菌清除。

Modulation of antigen-specific T and B cell responses influence bacterial clearance of non-typeable Haemophilus influenzae from the lung in a rat model.

作者信息

Kyd J M, Cripps A W

机构信息

Faculty of Medicine and Health Sciences, University of Newcastle, Callaghan, NSW, Australia.

出版信息

Vaccine. 1996 Oct;14(15):1471-8. doi: 10.1016/s0264-410x(96)00034-5.

Abstract

This study investigates antigen-specific B and T cell responses following mucosal immunization with the major outer membrane protein, P2, from non-typeable Haemophilus influenzae (NTHi) and the role of these responses in bacterial clearance following pulmonary challenge. Modification of the immunization preparation by the inclusion of sodium dodecyl sulphate (SDS) with the adjuvant, incomplete Freund's, differentially affects the T and B cell responses to the P2 antigen. Rats received an intra-Peyer's patch-immunization with P2 with or without the inclusion of 1% (w/v) SDS, were boosted via an intratracheal administration of P2 alone on day 14, and challenged with live NTHi in the lungs on day 21. There were significant differences in the rate of bacterial clearance between the different P2-immunized groups and the non-immune group. The inclusion of SDS with P2 resulted in enhanced bacterial clearance. This clearance corresponded to an enhancement of P2-specific lymphocyte proliferation by CD4+ T helper cells but a decrease (reduced approximately 75%) in anti-P2 IgG and IgA in both serum and bronchoalveolar lavage washings. P2-specific IgM levels were not altered. IgG subclass analysis indicated that the inclusion of SDS had caused a significant reduction in IgG2a and an increase in IgG1. The data indicates that the magnitude of antibody levels to P2 may not be as important as T cell responses in enhancing clearance of NTHi in the lung, in vivo, and that immunization targeting enhancement of antigen-specific T cells may be important to inducing effective immunity to NTHi.

摘要

本研究调查了用不可分型流感嗜血杆菌(NTHi)的主要外膜蛋白P2进行黏膜免疫后抗原特异性B细胞和T细胞反应,以及这些反应在肺部攻击后细菌清除中的作用。在免疫制剂中加入十二烷基硫酸钠(SDS)并与不完全弗氏佐剂一起使用,对T细胞和B细胞对P2抗原的反应有不同影响。大鼠接受经派伊尔结内注射含或不含1%(w/v)SDS的P2免疫,在第14天通过气管内单独注射P2进行加强免疫,并在第21天用活的NTHi进行肺部攻击。不同P2免疫组与非免疫组之间的细菌清除率存在显著差异。P2中加入SDS导致细菌清除增强。这种清除与CD4 + T辅助细胞增强P2特异性淋巴细胞增殖相对应,但血清和支气管肺泡灌洗洗液中抗P2 IgG和IgA减少(约减少75%)。P2特异性IgM水平未改变。IgG亚类分析表明,加入SDS导致IgG2a显著减少,IgG1增加。数据表明,在体内增强肺部NTHi清除方面,针对P2的抗体水平大小可能不如T细胞反应重要,并且针对增强抗原特异性T细胞的免疫对诱导针对NTHi的有效免疫可能很重要。

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