Regulatory T-cell expansion during chronic viral infection is dependent on endogenous retroviral superantigens

Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 02/2011; 108(9):3677-82. DOI: 10.1073/pnas.1100213108
Source: PubMed


Regulatory T cells (Treg) play critical roles in the modulation of immune responses to infectious agents. Further understanding of the factors that control Treg activation and expansion in response to pathogens is needed to manipulate Treg function in acute and chronic infections. Here we show that chronic, but not acute, infection of mice with lymphocytic choriomeningitis virus results in a marked expansion of Foxp3(+) Treg that is dependent on retroviral superantigen (sag) genes encoded in the mouse genome. Sag-dependent Treg expansion was MHC class II dependent, CD4 independent, and required dendritic cells. Thus, one unique mechanism by which certain infectious agents evade host immune responses may be mediated by endogenous Sag-dependent activation and expansion of Treg.

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    • "In addition to modulation of the conventional population of CD8+ and CD4+ T cells, Mtv have been demonstrated to influence the immune system during viral infection via expansion of a particular subset of CD4+ T cells expressing the transcription factor Foxp3. Murine infection with the clone 13 isolate of lymphocytic choriomeningitis virus (LCMV) represents a model of chronic viral infection, in which T cell exhaustion results in infection virtually for life (85, 86). Infection of mice with LCMV clone 13 resulted in the selective expansion of a TCR Vβ specific population of Foxp3+ regulatory T cells (Treg) (87). The expansion of TCR Vβ5+ Treg was determined to be MHC class II-dependent, CD4-independent, and secondary to stimulation by the Mtv-9-encoded Sag. "
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