MECHANISMS OF ANTIBODY-MEDIATED PROTECTION AGAINST LYMPHOCYTIC CHORIOMENINGITIS VIRUS-INFECTION - MOTHER-TO-BABY TRANSFER OF HUMORAL PROTECTION

MECHANISMS OF ANTIBODY-MEDIATED PROTECTION AGAINST LYMPHOCYTIC CHORIOMENINGITIS VIRUS-INFECTION - MOTHER-TO-BABY TRANSFER OF HUMORAL PROTECTION
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DOI:
10.1128/jvi.66.7.4252-4257.1992
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发表时间:
1992-07-01
影响因子:
5.4
通讯作者:
BUCHMEIER, MJ
BUCHMEIER, MJ
中科院分区:
医学2区
文献类型:
--
作者:
BALDRIDGE, JR;BUCHMEIER, MJ

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探讨了抗病毒抗体在抵抗淋巴细胞性脉络丛脑膜炎病毒(LCMV)感染中的作用。免疫血清和单克隆抗体可预防急性巨细胞病毒感染后致命的t细胞介导的免疫病理。此外,通过哺乳接受母源性抗LCMV抗体的10日龄和14日龄小鼠可以免受致命的LCMV攻击。利用抗lcmv单克隆抗体对这些抗病毒抗体提供保护的机制进行了详细的研究。这种保护直接与抗体在常规小鼠和裸鼠组织中降低病毒滴度的能力相关(K. E. Wright and M. J. Buchmeier, J. Virol. 65:3001-3006, 1991)。然而,这种减少并不仅仅是病毒中和活性的反映,因为并非所有在体外中和的抗体都具有保护作用。免疫球蛋白同型与保护之间也发现了相关性:所有保护性抗体都是免疫球蛋白G2a (IgG2a),而IgG1抗体则没有定位到相同的表位。保护似乎与Fc区控制的事件有关。保留体外中和活性的功能性F(ab’)2片段在体内不具有保护作用。此外,这种fc相关的功能与补体介导的细胞裂解无关,因为c5缺陷小鼠品系也受到保护。这些结果表明抗体在沙粒病毒感染保护中的作用,并表明一种独特的免疫球蛋白亚类IgG2a可能对这种保护至关重要。
The role of antiviral antibodies in resistance to lymphocytic choriomeningitis virus (LCMV) infection was explored. Immune serum and monoclonal antibodies prevented fatal T-cell-mediated immunopathology following acute 1,CMV infections. In addition, 10- and 14-day-old mice that received maternally derived anti-LCMV antibodies through nursing were protected from an otherwise lethal LCMV challenge. Detailed investigation of the mechanism(s) by which these antiviral antibodies provided protection was carried out by using anti-LCMV monoclonal antibodies. Protection correlated directly with the ability of the antibodies to reduce viral titers in the tissues of conventional (K. E. Wright and M. J. Buchmeier, J. Virol. 65:3001-3006, 1991) and nude mice. However, this reduction was not simply a reflection of virus neutralizing activity, since not all antibodies which neutralized in vitro were protective. A correlation was also found between immunoglobulin isotype and protection: all of the protective antibodies were immunoglobulin G2a (IgG2a), while IgG1 antibodies mapping to the same epitopes were not. Protection appeared to be associated with events controlled by the Fc region. Functional F(ab')2 fragments which retained in vitro neutralizing activity were not protective in vivo. Furthermore, this Fc-associated function was not related to complement-mediated cell lysis, since C5-deficient mouse strains were also protected. These results suggest a role for antibody in protection from arenavirus infections and indicate that a distinct immunoglobulin subclass, IgG2a, may be essential for this protection.