Selective enhancement of systemic Th1 immunity in immunologically immature rats with an orally administered bacterial extract

Selective enhancement of systemic Th1 immunity in immunologically immature rats with an orally administered bacterial extract
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DOI:
10.1128/iai.69.6.3719-3727.2001
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发表时间:
2001-06-01
影响因子:
3.1
通讯作者:
Holt, PG
Holt, PG
中科院分区:
医学2区
文献类型:
--
作者:
Bowman, LM;Holt, PG

文献摘要

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在第一周的生活与可溶性抗原引发的婴儿大鼠显示成人同等水平的辅助性T细胞2(Th 2)依赖性免疫记忆的发展所揭示的生产的第二免疫球蛋白G1(IgG 1)抗体反应随后的挑战,但在相反的成年人未能引发的Th 1依赖性IgG 2b的反应。我们证明,这种免疫功能中的Th 2偏倚可以通过向新生儿口服细菌提取物(Broncho-Vaxom OM-85)来纠正,所述细菌提取物包含几种常见呼吸道细菌病原体的冻干组分。给予OM-85的动物显示出原发性和继发性IgG 2b应答的选择性上调,伴随着γ干扰素增加和白细胞介素-IL产生减少(抗原特异性和多克隆),以及对攻击抗原的Th 1依赖性迟发型超敏反应的发展能力增加。我们假设细菌提取物通过增强出生后Th 1功能成熟的过程发挥作用,Th 1功能通常由胃肠道肠道微生物菌群的刺激驱动。
Infant rats primed during the first week of life with soluble antigen displayed adult-equivalent levels of T-helper 2 (Th2)-dependent immunological memory development as revealed by production of secondary immunoglobulin G1 (IgG1) antibody responses to subsequent challenge, but in contrast to adults failed to prime for Th1-dependent IgG2b responses. We demonstrate that this Th2 bias in immune function can be redressed by oral administration to neonates of a bacterial extract (Broncho-Vaxom OM-85) comprising lyophilized fractions of several common respiratory tract bacterial pathogens. Animals given OM-85 displayed a selective upregulation in primary and secondary IgG2b responses, accompanied by increased gamma interferon and decreased interleukin-il production (both antigen specific and polyclonal), and increased capacity for development of Th1-dependent delayed hypersensitivity to the challenge antigen. We hypothesize that the bacterial extract functions via enhancement of the process of postnatal maturation of Th1 function, which is normally driven by stimuli from the gastrointestinal commensal microflora.