Induction of granulysin and perforin cytolytic mediator expression in 10-week-old infants vaccinated with BCG at birth.

Induction of granulysin and perforin cytolytic mediator expression in 10-week-old infants vaccinated with BCG at birth.
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DOI:
10.1155/2011/438463
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发表时间:
2011
影响因子:
--
通讯作者:
Ress S
Ress S
中科院分区:
其他
文献类型:
--
作者:
Semple PL;Watkins M;Davids V;Krensky AM;Hanekom WA;Kaplan G;Ress S

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背景资料。虽然出生时接种卡介苗(BCG)可以预防严重的儿童结核病,但关于卡介苗诱导的免疫反应中的哪些成分介导了这种保护,还没有达成共识。然而,在细胞毒性T淋巴细胞和自然杀伤细胞(NK)的颗粒中发现的颗粒溶素和穿孔素可以杀死细胞内的分枝杆菌,并与抗结核分枝杆菌有关。方法:研究方法。我们比较了出生时接种日本或丹麦卡介苗的10周大婴儿脐带血和外周血中粒溶素和穿孔素细胞溶解分子的细胞表达,无论是皮内注射还是经皮注射。结果。脐血中仅CD56+NK细胞结构性表达颗粒溶素和穿孔素。卡介苗体外刺激可上调CD4+和CD8+脐血细胞中这些溶细胞介质的表达,而PPD则无此作用。新生儿接种卡介苗后,卡介苗和PPD均可诱导CD4+和CD8+T细胞表达颗粒溶素和穿孔素。不同接种途径和不同品系的细胞溶解分子表达无明显差异。结论。脐血NK细胞结构性表达穿孔素和颗粒溶素可能提供天然免疫,而卡介苗诱导的这些溶细胞介质的表达可能有助于保护新生儿免受结核病的侵袭。
Background. While vaccination at birth with Mycobacterium bovis Bacilli Calmette-Guérin (BCG) protects against severe childhood tuberculosis, there is no consensus as to which components of the BCG-induced immune response mediate this protection. However, granulysin and perforin, found in the granules of cytotoxic T lymphocytes and Natural Killer (NK) cells, can kill intracellular mycobacteria and are implicated in protection against Mycobacterium tuberculosis. Methods. We compared the cellular expression of granulysin and perforin cytolytic molecules in cord blood and peripheral blood from 10-week-old infants vaccinated at birth with either Japanese or Danish BCG, administered either intradermally or percutaneously. Results. In cord blood, only CD56+ NK cells expressed granulysin and perforin constitutively. These cytolytic mediators were upregulated in CD4+ and CD8+ cord blood cells by ex vivo stimulation with BCG but not with PPD. Following BCG vaccination of neonates, both BCG and PPD induced increased expression of granulysin and perforin by CD4+ and CD8+ T cells. There was no difference in expression of cytolytic molecules according to vaccination route or strain. Conclusions. Constitutive expression of perforin and granulysin by cord blood NK-cells likely provides innate immunity, while BCG vaccination-induced expression of these cytolytic mediators may contribute towards protection of the neonate against tuberculosis.
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