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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • DNA-Binding Proteins / deficiency*
  • DNA-Binding Proteins / immunology
  • Diphtheria Toxin / pharmacology
  • Forkhead Transcription Factors / metabolism*
  • HIV Infections / immunology*
  • HIV-1 / drug effects
  • HIV-1 / immunology*
  • HIV-1 / physiology
  • Humans
  • Immunoglobulin gamma-Chains / genetics*
  • Immunoglobulin gamma-Chains / metabolism
  • Interleukin-2 / pharmacology
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Lymphocyte Depletion
  • Mice
  • Mice, Knockout
  • Recombinant Fusion Proteins / pharmacology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / virology*
  • Virus Replication / drug effects


  • DNA-Binding Proteins
  • Diphtheria Toxin
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Immunoglobulin gamma-Chains
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Rag2 protein, mouse
  • Recombinant Fusion Proteins
  • denileukin diftitox