FoxP3+CD4+ regulatory T cells play an important role in acute HIV-1 infection in humanized Rag2-/-{gamma}C-/-mice in vivo

Qi Jiang, Liguo Zhang, Rui Wang, Jerry Jeffrey, Michael L. Washburn, Dedeke Brouwer, Selena Barbour, Grigoriy I. Kovalev, Derya Unutmaz, Lishan Su

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)

Abstract

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 -/-γC -/- (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.

Original languageEnglish
Pages (from-to)2858-2868
Number of pages11
JournalBlood
Volume112
Issue number7
DOIs
Publication statusPublished - 1 Oct 2008
Externally publishedYes

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