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

Inês Antunes,Mauro Tolaini,Adrien Kissenpfennig,Michihiro Iwashiro,Kagemasa Kuribayashi,Bernard Malissen,Kim Hasenkrug,George Kassiotis

doi:10.1016/j.immuni.2008.09.016

Inês Antunes, Mauro Tolaini + Show 6 more

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https://doi.org/10.1016/j.immuni.2008.09.016

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SummaryChronic 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-γ-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-γ production by FV-specific CD4+ T cells. We further showed that the T cell receptor (TCR) repertoire of transgenic Treg cells expressing the β 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.

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A cardinal feature of adaptive immunity is that its response to infection is proportional to the pathogen load and antigen presentation, which regulate the expansion and contraction of antigen-specific lymphocytes (Zinkernagel and Hengartner, 2001)
Using unresolving noncytopathic Friend virus (FV) infection in mice, we showed that unregulated CD4+ T cell response to FV caused IFN-g-mediated bone marrow pathology and anemia
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-g production by FV-specific CD4+ T cells

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Introduction

A cardinal feature of adaptive immunity is that its response to infection is proportional to the pathogen load and antigen presentation, which regulate the expansion and contraction of antigen-specific lymphocytes (Zinkernagel and Hengartner, 2001). An effective immune response, which leads to pathogen control or clearance, is self-limiting. Strong and lasting immune responses, which are ineffective in pathogen clearance, may be damaging to the host (Zinkernagel and Hengartner, 2001). Excessive or ineffective immune responses are characteristic of certain chronic viral infections, and their control is essential for the prevention of host tissue damage (Welsh and Selin, 2002; Zinkernagel, 2002; Guidotti and Chisari, 2006). Several different mechanisms may operate, separately or in concert, to limit immune pathology. The reactivity of antigen-specific T cells can be actively regulated by potent suppressive mediators or specialized cell types, such as naturally occurring regulatory T (Treg) cells (Mills, 2004; Rouse et al, 2006; Belkaid, 2007)

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