Effect of cytokines on HIV-induced depletion of thymocytes in vivo

Uíttenbogaart, Christel H.; Boscardin, W. John; Anisman-Posner, Deborah; Koka, Prasad S; Bristol, Gregory; Zack, Jerome A.

doi:10.1097/00002030-200007070-00003

Cited by 37 publications

(48 citation statements)

References 52 publications

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“…Given the profound effects of IL-7 on the survival of human thymocytes, it is possible that IL-7 might prevent or attenuate HIV-mediated destruction of the thymus. However, IL-7 has also been shown to enhance HIV replication and cytopathicity (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). Thus, it is unclear whether IL-7 might enhance thymocyte survival in the HIVinfected thymus or, alternatively, enhance HIV-mediated thymocyte destruction.…”

Section: Effects Of Il-7 On Hiv-infected and Uninfected Thymus In Scimentioning

confidence: 99%

“…Nevertheless, the fact that IL-7 has been shown to enhance HIV infection, replication, and cytopathicity (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32) has raised some concerns regarding its potential use in HIV disease. We sought to identify more specifically the effects of IL-7 on human thymocyte survival and to study the effects of IL-7 on the HIV-infected human thymus.…”

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confidence: 99%

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Effects of IL-7 on Early Human Thymocyte Progenitor Cells In Vitro and in SCID-hu Thy/Liv Mice

Napolitano

Stoddart

Hanley

et al. 2003

The Journal of Immunology

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IL-7 is a critical component of thymopoiesis in animals and has recently been shown to play an important role in T cell homeostasis. Although there is increasing interest in the use of IL-7 for the treatment of lymphopenia caused by the HIV type 1, evidence that IL-7 may accelerate HIV replication has raised concerns regarding its use in this setting. We sought to identify the effects of IL-7 on human thymocyte survival and to determine the impact of IL-7 administration on in vivo HIV infection of the human thymus. Using in vitro analysis, we show that IL-7 provides potent anti-apoptotic and proliferative signals to early thymocyte progenitors. Analysis of CD34+ subpopulations demonstrates that surface IL-7 receptor is expressed on most CD34highCD5+CD1a− thymocytes and that this subpopulation appears to be one of the earliest maturation stages responsive to the effects of IL-7. Thus, IL-7 provides survival signals to human thymocytes before surface expression of CD1a. CD4+CD8+ thymocytes are relatively unresponsive to IL-7, although IL-7 protects these cells from dexamethasone-induced apoptosis. IL-7 has a predominantly proliferative effect on mature CD4+CD3+CD8− and CD8+CD3+CD4− thymocytes. In contrast to the in vitro findings, we observe that in vivo administration of IL-7 to SCID-hu Thy/Liv mice does not appear to enhance thymocyte survival nor does it appear to accelerate HIV infection. Given the growing interest in the use of IL-7 for the treatment of human immunodeficiency, these findings support additional investigation into its in vivo effects on thymopoiesis and HIV infection.

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Section: Effects Of Il-7 On Hiv-infected and Uninfected Thymus In Scimentioning

confidence: 99%

mentioning

confidence: 99%

Effects of IL-7 on Early Human Thymocyte Progenitor Cells In Vitro and in SCID-hu Thy/Liv Mice

Napolitano

Stoddart

Hanley

et al. 2003

The Journal of Immunology

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“…The tissue was cut into small pieces and RBC were removed by NH 4 Cl-Tris lysis and passed over a cell strainer to generate a single-cell suspension of thymocytes as previously described (8). The cells were washed in PBS and serum-free medium (AT-IMDM) consisting of IMDM (Omega Scientific, Tarzana, CA) supplemented with delipidated BSA (Sigma-Aldrich) at 1100 g/ml, transferrin (Sigma-Aldrich) at 85 g/ml, 2 mM glutamine, and penicillin/streptomycin at 25 U/25 g/ml (8,38). The thymocytes were resuspended at 2 ϫ 10 5 cells/ml in AT-IMDM for HIV infection (see below).…”

Section: Thymocyte and Pbmc Preparationmentioning

confidence: 99%

“…TCR␥␦ thymocytes, TCR␥␦-depleted thymocytes, and total thymocytes were infected in vitro and cultured as previously described for total thymocytes (8,38). Briefly, 2 ϫ 10 5 freshly isolated, nonstimulated thymocytes were incubated with 7 ng of viral p24 in the presence of 10 g/ml polybrene (Sigma-Aldrich) for 1 h at 37°C.…”

Section: Hiv-1 Infection Of Scid-hu Mice and Postnatal Thymocytesmentioning

confidence: 99%

TCRγδ+ and CD161+ Thymocytes Express HIV-1 in the SCID-hu Mouse, Potentially Contributing to Immune Dysfunction in HIV Infection

Gurney

Yang

Wilson

et al. 2002

The Journal of Immunology

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The vast diversity of the T cell repertoire renders the adaptive immune response capable of recognizing a broad spectrum of potential antigenic peptides. However, certain T cell rearrangements are conserved for recognition of specific pathogens, as is the case for TCRγδ cells. In addition, an immunoregulatory class of T cells expressing the NK receptor protein 1A (CD161) responds to nonpeptide Ags presented on the MHC-like CD1d molecule. The effect of HIV-1 infection on these specialized T cells in the thymus was studied using the SCID-hu mouse model. We were able to identify CD161-expressing CD3+ cells but not the CD1d-restricted invariant Vα24/Vβ11/CD161+ NK T cells in the thymus. A subset of TCRγδ cells and CD161-expressing thymocytes express CD4, CXCR4, and CCR5 during development in the thymus and are susceptible to HIV-1 infection. TCRγδ thymocytes were productively infectable by both X4 and R5 virus, and thymic HIV-1 infection induced depletion of CD4+ TCRγδ cells. Similarly, CD4+CD161+ thymocytes were depleted by thymic HIV-1 infection, leading to enrichment of CD4−CD161+ thymocytes. Furthermore, compared with the general CD4-negative thymocyte population, CD4−CD161+ NK T thymocytes exhibited as much as a 27-fold lower frequency of virus-expressing cells. We conclude that HIV-1 infection and/or disruption of cells important in both innate and acquired immunity may contribute to the overall immune dysfunction seen in HIV-1 disease.

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“…Depletion of IFN -γ levels in presence of IL-4 has been observed in the thymocytes of HIV infected individuals (32). This depletion occurs since the absolute numbers of CD4 + T cells decrease in the thymocytes.…”

Section: Discussionmentioning

confidence: 95%

Estimation of mRNA levels of interleukin (IL)-10, tumor necrosis factor (TNF)-α, IL-4 and interferon (IFN)-γ in HIV infected children in Mumbai

Kothari

Deshmukh

2006

Indian J Clin Biochem

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Effect of cytokines on HIV-induced depletion of thymocytes in vivo

Abstract: Cytokines such as IL-2 and IFN-gamma maintain immature thymocytes without increasing viral load and may be useful as adjuncts to improve immune reconstitution after HIV infection.

Cited by 37 publications

References 52 publications

Effects of IL-7 on Early Human Thymocyte Progenitor Cells In Vitro and in SCID-hu Thy/Liv Mice

Effects of IL-7 on Early Human Thymocyte Progenitor Cells In Vitro and in SCID-hu Thy/Liv Mice

TCRγδ+ and CD161+ Thymocytes Express HIV-1 in the SCID-hu Mouse, Potentially Contributing to Immune Dysfunction in HIV Infection

Estimation of mRNA levels of interleukin (IL)-10, tumor necrosis factor (TNF)-α, IL-4 and interferon (IFN)-γ in HIV infected children in Mumbai

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