In vivo depletion of CD4(+)CD25(hi) regulatory T cells is associated with improved antiviral responses in cats chronically infected with feline immunodeficiency virus

体内 CD4(+)CD25(hi) 调节性 T 细胞的耗竭与慢性感染猫免疫缺陷病毒的猫的抗病毒反应改善有关

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作者:S Rochelle Mikkelsen, Stacie K Reckling, Erin A Egan, Gregg A Dean

Abstract

Regulatory T (Treg) cells are activated and suppress immune responses during infection, and are characterized as CD4(+)CD25(hi)FOXP3(+). Ex vivo studies demonstrate that Treg cells potentially suppress anti-HIV-1 T cell responses. Lentivirus-induced CD4(+)CD25(hi) Treg cells were first described in feline immunodeficiency virus (FIV)-infected cats. In the present study we demonstrate that anti-feline CD25 monoclonal antibody (mAb) therapy depletes Treg cells in FIV-infected cats for 4 weeks and does not exacerbate viral replication or proinflammatory cytokine production. Significant FIV-specific immune responses are revealed in Treg cell-depleted cats. These anti-FIV effector cells exist prior to Treg cell depletion and are not expanded while Treg cells are depleted. Importantly, cats receiving the Treg cell-depleting mAb are able to produce a robust humoral response to new antigen. We propose that short-term in vivo Treg cell depletion during chronic HIV-1 infection could provide a window of opportunity for therapeutic vaccination in individuals with controlled viral replication.

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