Antunes Inês, Tolaini Mauro, Kissenpfennig Adrien, Iwashiro Michihiro, Kuribayashi Kagemasa, Malissen Bernard, Hasenkrug Kim, Kassiotis George
Divisions of Immunoregulation, The MRC National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK.
Immunity. 2008 Nov 14;29(5):782-94. doi: 10.1016/j.immuni.2008.09.016.
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.
造血系统的慢性病毒感染与骨髓功能障碍有关，病毒介导的效应和免疫介导的效应都可能导致这种情况。利用小鼠中无法消除的非细胞病变型弗氏病毒（FV）感染，我们发现对FV不受调控的CD4(+) T细胞反应会导致IFN-γ介导的骨髓病变和贫血。重要的是，骨髓病变是由调节性T（Treg）细胞相对不足引发的，添加Treg细胞可预防这种情况，Treg细胞可抑制FV特异性CD4(+) T细胞产生局部IFN-γ。我们进一步表明，表达FV特异性TCRβ链的转基因Treg细胞的T细胞受体（TCR）库几乎没有FV特异性克隆。此外，病毒非特异性Treg细胞可有效抑制病毒特异性CD4(+) T细胞诱导的贫血。因此，足够数量的多克隆Treg细胞可能为慢性病毒感染中的骨髓病变提供实质性保护。
