Required early complement activation in contact sensitivity with generation of local C5-dependent chemotactic activity, and late T cell interferon gamma: a possible initiating role of B cells.

Required early complement activation in contact sensitivity with generation of local C5-dependent chemotactic activity, and late T cell interferon gamma: a possible initiating role of B cells.
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与局部C5依赖性趋化活性和晚期T细胞干扰素γ的产生的接触敏感性中需要早期补体激活:B细胞的可能启动作用。

DOI:
10.1084/jem.186.7.1015
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发表时间:
1997-10-06
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Askenase PW
Askenase PW
中科院分区:
其他
文献类型:
--
作者:
Tsuji RF;Geba GP;Wang Y;Kawamoto K;Matis LA;Askenase PW

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补体(C)是天然免疫的重要组成部分,最近也被证明参与诱导获得性B细胞体液免疫。在这项研究中,我们提出的证据表明,C也参与获得性T细胞免疫。我们发现,C参与了接触敏感性(CS)和迟发型超敏反应(DTH)的传出激发相的早期事件。因此,CS和DTH抑制C-受体阻滞剂,可溶性重组C受体-1(sCR 1),当给药前30分钟,但不是3小时后局部抗原的挑战。在C组分中,局部C5被认为是诱发CS的关键,因为局部施用抗C5单克隆抗体或局部注射C-消耗眼镜蛇毒因子也抑制CS和DTH。这些发现与我们先前使用先天性C5缺陷小鼠发现的C5对CS诱导的重要性一致。为了剖析CS中C依赖性的机制,我们证明了局部增加的早期巨噬细胞趋化活性(可能是C5 a)在不断发展的CS皮肤提取物中,以及IFN-γ的后期加工,都受到抗C治疗的抑制。此外,组织学分析表明,白细胞募集到CS耳部位是类似的C-依赖性。此外,通过证明B细胞缺陷小鼠中CS反应受损,提示了B细胞衍生的C固定免疫球蛋白的起始作用。总之,这些结果表明,C可能通过B细胞产物局部激活,这是引发CS所需的逐步事件的重要早期组成部分,导致局部产生C5依赖性巨噬细胞趋化活性,随后产生IFN-γ,随后导致细胞浸润,从而发展为T细胞依赖性CS。
Complement (C) is an important component of innate immunity, and was also shown recently to participate in induction of acquired B cell humoral immunity. In this study, we present evidence that C also participates in acquired T cell immunity. We found that C was involved in early events of the efferent elicitation phase of contact sensitivity (CS), and delayed-type hypersensitivity (DTH). Thus, CS and DTH were inhibited by administration of a C-blocker, soluble recombinant C receptor-1 (sCR1), when given 30 min before, but not 3 h after local antigen challenge. Among C components, local C5 were thought crucial to elicitation of CS, since local administration of anti-C5 monoclonal antibodies or locally injected C-depleting cobra venom factor also inhibited CS and DTH. These findings were consistent with our previous finding of the importance of C5 for CS elicitation, using congenitally C5-deficient mice. To dissect the mechanism of C dependence in CS, we demonstrated that locally increased early macrophage chemotactic activity (probably C5a) in evolving CS skin extracts, as well as late elaboration of IFN-γ, were both inhibited by anti-C treatment. In addition, histological analysis showed that leukocyte recruitment into CS ear sites was similarly C-dependent. Furthermore, an initiating role of B cell–derived C-fixing immunoglobulin was suggested by demonstration of impaired CS responses in B cell–deficient mice. In summary, these results suggest that C was activated locally, perhaps via a B cell product, in an important early component of the stepwise events necessary to elicit CS, leading to local production of C5-dependent macrophage chemotactic activity and later IFN-γ, and subsequently leading to cell infiltration, for development of T cell–dependent CS.
DOI: 10.1111/1523-1747.ep12363337
发表时间: 1996-09-01
影响因子: 6.5
作者:
Abe, M;Kondo, T;Fairchild, RL
通讯作者: Fairchild, RL
补体受体特异性单克隆抗体对抗体反应的体内抑制。
DOI: 10.1084/jem.172.2.665
发表时间: 1990-08-01
影响因子: 15.3
作者:
Heyman, B;Wiersma, E J;Kinoshita, T
通讯作者: Kinoshita, T
DOI: 10.1016/0167-5699(91)90009-i
发表时间: 1991-09-01
期刊: IMMUNOLOGY TODAY
影响因子: --
作者:
FRANK, MM;FRIES, LF
通讯作者: FRIES, LF
DOI: 10.1126/science.272.5258.50
发表时间: 1996-04-05
期刊: SCIENCE
影响因子: 56.9
作者:
Fearon, DT;Locksley, RM
通讯作者: Locksley, RM
DOI: 10.1126/science.271.5247.348
发表时间: 1996-01-19
期刊: SCIENCE
影响因子: 56.9
作者:
Dempsey, PW;Allison, MED;Fearon, DT
通讯作者: Fearon, DT