Retrovirus-specificity of regulatory T cells is neither present nor required in preventing retrovirus-induced bone marrow immune pathology.
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.
Antunes
Inês
I
Divisions of Immunoregulation, The MRC National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK.
Tolaini
Mauro
M
Kissenpfennig
Adrien
A
Iwashiro
Michihiro
M
Kuribayashi
Kagemasa
K
Malissen
Bernard
B
Hasenkrug
Kim
K
Kassiotis
George
G
D019264:Adoptive Transfer; D000740:Anemia / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D000818:Animals; D001853:Bone Marrow / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002908:Chronic Disease; D005622:Friend murine leukemia virus / Q000276:immunology* / Q000472:pathogenicity; D055785:Gene Knockdown Techniques; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D012192:Retroviridae Infections / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma