Impaired Antibody Response Causes Persistence of Prototypic T Cell-Contained Virus

被引：80

作者：

Bergthaler, Andreas ^{[1
,2
]}

Flatz, Lukas ^{[1
,2
]}

Verschoor, Admar ^{[2
]}

Hegazy, Ahmed N. ^{[2
]}

Holdener, Martin ^{[2
]}

Fink, Katja ^{[2
]}

Eschli, Bruno ^{[2
]}

Merkler, Doron ^{[3
]}

Sommerstein, Rami ^{[1
,4
]}

Horvath, Edit ^{[2
]}

Fernandez, Marylise ^{[1
,4
]}

Fitsche, Andre ^{[2
]}

Senn, Beatrice M. ^{[2
]}

Verbeek, J. Sjef ^{[5
]}

Odermatt, Bernhard ^{[2
]}

Siegrist, Claire-Anne ^{[1
,4
,6
]}

Pinschewer, Daniel D. ^{[1
,2
,4
]}

机构：

[1] Univ Geneva, Dept Pathol & Immunol, Geneva, Switzerland

[2] Univ Zurich Hosp, Inst Clin Pathol, CH-8091 Zurich, Switzerland

[3] Univ Gottingen, Dept Neuropathol, D-3400 Gottingen, Germany

[4] Univ Geneva, WHO Collaborating Ctr Neonatal Vaccinol, Geneva, Switzerland

[5] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands

[6] Univ Geneva, Dept Pediat, Geneva, Switzerland

来源：

PLOS BIOLOGY | 2009年 / 7卷 / 04期

基金：

瑞士国家科学基金会;

关键词：

LYMPHOCYTIC CHORIOMENINGITIS VIRUS; HEPATITIS-C VIRUS; IMMUNODEFICIENCY-VIRUS; NEUTRALIZING ANTIBODIES; DEFICIENT MICE; ADOPTIVE IMMUNOTHERAPY; IMMUNE-RESPONSES; INFECTED MICE; IN-VIVO; B-CELLS;

D O I：

10.1371/journal.pbio.1000080

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

CD8 T cells are recognized key players in control of persistent virus infections, but increasing evidence suggests that assistance from other immune mediators is also needed. Here, we investigated whether specific antibody responses contribute to control of lymphocytic choriomeningitis virus (LCMV), a prototypic mouse model of systemic persistent infection. Mice expressing transgenic B cell receptors of LCMV-unrelated specificity, and mice unable to produce soluble immunoglobulin M (IgM) exhibited protracted viremia or failed to resolve LCMV. Virus control depended on immunoglobulin class switch, but neither on complement cascades nor on Fc receptor gamma chain or Fc gamma receptor IIB. Cessation of viremia concurred with the emergence of viral envelope-specific antibodies, rather than with neutralizing serum activity, and even early nonneutralizing IgM impeded viral persistence. This important role for virus-specific antibodies may be similarly underappreciated in other primarily T cell-controlled infections such as HIV and hepatitis C virus, and we suggest this contribution of antibodies be given consideration in future strategies for vaccination and immunotherapy.

引用

页码：789 / 799

页数：11

共 74 条

[1] Maintenance of memory CTL responses by T helper cells and CD40-CD40 ligand: antibodies provide the key [J].