MRC National Institute for Medical Research, London
Science for Health
Retrovirus-induced pathology prevented by virus-nonspecific regulatory T cells
14 November 2008
Bone marrow pathology is a common feature of retroviral infection in humans. Bone marrow dysfunction is responsible for the development of anaemia in approximately 60% and 90% of acute and chronic HIV-1 infections, respectively, and contributes to other cytopenias, including lymphopenia. It is currently unclear whether bone marrow pathology in HIV-1 infection results from direct cytopathic effects of the virus on bone marrow precursors or from indirect immune-mediated effects, and it is likely that its origin is multifactorial.
George Kassiotis (pictured), from NIMR's Division of Immunoregulation, worked with collaborators in France, Japan and the USA to show that, in a mouse model for retroviral infection, bone marrow pathology and anaemia are caused not by cytopathic effects of the virus but by virus-specific CD4+ T cells responding to the virus in the local bone marrow microenvironment. The research has also shown that the severity of anaemia critically depends on the balance between virus-specific pathogenic CD4+ T cells and Treg cells, a small subset of T cells with naturally-endowed suppressive activity against excessive T cell responses. Surprisingly, pathogenic CD4+ T cells and Treg cells differ dramatically in their requirements for direct recognition of viral antigens; efficient suppression of virus-induced bone marrow pathology by Treg cells does not necessitate direct viral antigen recognition.
One important implication of our findings is that, in contrast to pathology induced by direct cytopathic effects of retroviral infection, T cell-mediated immune pathology is amenable to immune regulation. Bone marrow pathology in retroviral infection is triggered by relative insufficiency in Treg cells and, more importantly, is prevented by added Treg cells. The pathology-inducing T cells react to the virus; the protective Treg cells do not. Our aim is to find out what activates Treg cells in this infection, as this will help shift the balance between pathogenic T cells and protective Treg cells in favour of the host.
George Kassiotis
Original article
The research findings are published in full in:
Antunes I, Tolaini M, Kissenpfennig A, Iwashiro M, Kuribayashi K, Malissen B, Hasenkrug K, Kassiotis G.
Retrovirus-Specificity of Regulatory T Cells Is Neither Present nor Required in Preventing Retrovirus-Induced Bone Marrow Immune Pathology
Immunity, 29 p 782-794. PubMed abstract
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