Functional Impairment of CD8+ T Cells by Regulatory T Cells during Persistent Retroviral Infection

Institut für Virologie des Universitätsklinikums, 45122 Essen, Germany.
Immunity (Impact Factor: 19.75). 04/2004; 20(3):293-303. DOI: 10.1016/S1074-7613(04)00054-8
Source: PubMed

ABSTRACT The establishment of viral persistence generally requires evasion of the host CD8(+) T cell response. Here we describe a form of evasion wherein the CD8(+) T cells are fully capable of recognizing their cognate antigen but their effector functions are suppressed by regulatory T cells. Virus-specific CD8(+) T cells adoptively transferred into mice persistently infected with Friend virus proliferated and appeared activated, but failed to produce IFNgamma or reduce virus loads. Cotransfer experiments revealed that a subpopulation of CD4(+) T cells from persistently infected mice suppressed IFNgamma production by the CD8(+) T cells. Treatment of persistently infected mice with anti-GITR antibody to ameliorate suppression by regulatory T cells significantly improved IFNgamma production by transferred CD8(+) T cells and allowed a significant reduction in viral loads. The results indicate that CD4(+) regulatory T cells contribute to viral persistence and demonstrate an immunotherapy for treating chronic retroviral infections.

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Available from: Leonard H Evans, Jul 02, 2015
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