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: 9.81). 02/2011; 108(9):3677-82. DOI: 10.1073/pnas.1100213108
Source: PubMed

ABSTRACT 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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Available from: Deborah Dacek Glass, Aug 10, 2015
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    • "WT and DEREG mice were treated with DT on days 10 and 11 following CL-13 infection. Recent work has indicated that the number of Tregs increase after day 10 post-infection Punkosdy et al., 2011, thus day 10 was chosen for depletion. Weight loss and survival were monitored daily following infection (Fig. 6). "
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    • "During chronic lymphocytic choriomeningitis virus (LCMV) infection, Treg cells have been shown to recognize a self-antigen rather than a virus-specific antigen (Punkosdy et al., 2011). This finding may reflect the fact that thymically derived Treg cells are selected by high-affinity interactions with self-antigens within the thymus (Bautista et al., 2009; DiPaolo and Shevach, 2009) and therefore have a propensity for recognizing self-antigens in the periphery (Hsieh et al., 2004, 2006; Killebrew et al., 2011; Korn et al., 2007). "
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