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Blood. 2008 Oct 1;112(7):2858-68. doi: 10.1182/blood-2008-03-145946. Epub 2008 Jun 10.

FoxP3+CD4+ regulatory T cells play an important role in acute HIV-1 infection in humanized Rag2-/-gammaC-/- mice in vivo.

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Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, USA.


The role of FoxP3(+)CD4(+) regulatory T (Treg) cells in HIV-1 disease in vivo is poorly understood due to the lack of a robust model. We report here that CD4(+)FoxP3(+) T cells are developed in all lymphoid organs in humanized Rag2(-/-)gammaC(-/-) (DKO-hu HSC) mice and they display both Treg phenotype and Treg function. These FoxP3(+) Treg cells are preferentially infected and depleted by a pathogenic HIV-1 isolate in HIV-infected DKO-hu HSC mice; and depletion of Treg cells is correlated with induction of their apoptosis in vivo. When CD4(+)CD25(+/hi) Treg cells are depleted with the IL-2-toxin fusion protein (denileukin diftitox), HIV-1 infection is significantly impaired. This is demonstrated by reduced levels of productively infected cells in lymphoid organs and lower plasma viremia. Therefore, FoxP3(+) Treg cells are productively infected and play an important role in acute HIV-1 infection in vivo. The DKO-hu HSC mouse will be a valuable model to study human Treg functions and their role in HIV-1 pathogenesis in vivo.

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