FoxP3+CD4+ regulatory T cells play an important role in acute HIV-1 infection in humanized Rag2-/-gammaC-/- mice in vivo.
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.
Jiang
Qi
Q
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, USA.
Zhang
Liguo
L
Wang
Rui
R
Jeffrey
Jerry
J
Washburn
Michael L
ML
Brouwer
Dedeke
D
Barbour
Selena
S
Kovalev
Grigoriy I
GI
Unutmaz
Derya
D
Su
Lishan
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000276:immunology; D004167:Diphtheria Toxin / Q000494:pharmacology; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007142:Immunoglobulin gamma-Chains / Q000235:genetics* / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D018345:Mice, Knockout; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects
D004268:DNA-Binding Proteins; D004167:Diphtheria Toxin; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007142:Immunoglobulin gamma-Chains; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; C499308:Rag2 protein, mouse; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox