Retrovirus-Specificity of Regulatory T Cells Is Neither Present nor Required in Preventing Retrovirus-Induced Bone Marrow Immune Pathology

被引:47
作者
Antunes, Ines [1 ]
Tolaini, Mauro [2 ]
Kissenpfennig, Adrien [4 ]
Iwashiro, Michihiro [6 ]
Kuribayashi, Kagemasa [5 ]
Malissen, Bernard [4 ]
Hasenkrug, Kim [3 ]
Kassiotis, George [1 ]
机构
[1] Natl Inst Med Res, MRC, Div Immunoregulat, London NW7 1AA, England
[2] Natl Inst Med Res, MRC, Div Mol Immunol, London NW7 1AA, England
[3] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA
[4] Univ Aix Marseille 2, CNRS, INSERM, Ctr Immunol Marseille Luminy, F-13288 Marseille 09, France
[5] Tazuke Kofukai Med Res Inst, Osaka 5308480, Japan
[6] Kyoto Univ, Fac Med, Dept Oral & Maxillofacial Surg, Kyoto 6068507, Japan
基金
英国医学研究理事会;
关键词
D O I
10.1016/j.immuni.2008.09.016
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Chronic viral infections of the hematopoietic system are associated with bone marrow dysfunction, to which both virus-mediated and immune-mediated effects may contribute. Using unresolving noncytopathic Friend virus (FV) infection in mice, we showed that unregulated CD4+ T cell response to FV caused IFN-gamma-mediated bone marrow pathology and anemia. Importantly, bone marrow pathology was triggered by relative insufficiency in regulatory T (Treg) cells and was prevented by added Treg cells, which suppressed the local IFN-gamma production by FV-specific CD4(+) T cells. We further showed that the T cell receptor (TCR) repertoire of transgenic Treg cells expressing the beta chain of an FV-specific TCR was virtually devoid of FV-specific clones. Moreover, anemia induction by virus-specific CD4(+) T cells was efficiently suppressed by virus-nonspecific Treg cells. Thus, sufficient numbers of polyclonal Treg cells may provide substantial protection against bone marrow pathology in chronic viral infections.
引用
收藏
页码:782 / 794
页数:13
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