IL-7 differentially regulates cell cycle progression and HIV-1-based vector infection in neonatal and adult CD4<sup>+</sup>T cells

Dardalhon, Valérie; Jaleco, Sara; Kinet, Sandrina; Herpers, Bjorn L.; Steinberg, Marcos; Ferrand, Christophe; Froger, Delphine; Leveau, C; Tiberghien, Pierre; Charneau, Pierre; Noraz, Nelly; Taylor, Naomi

doi:10.1073/pnas.161272698

Cited by 93 publications

(97 citation statements)

References 49 publications

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“…Our findings suggest that the decreased level of serum IL-7 in the elderly could be responsible for the decreased EM CD4 ϩ T cells. Although the mechanism for the effect of IL-7 on T cells is not fully understood, such an effect is unlikely to be secondary to increased cell proliferation, because IL-7 does not induce the proliferation of naive and memory human CD4 ϩ T cells (13,36). Likewise, we found that IL-7 did not induce the proliferation of human CD4 ϩ T cells (data not shown).…”

Section: Discussionmentioning

confidence: 65%

Age-Associated Change in the Frequency of Memory CD4+ T Cells Impairs Long Term CD4+ T Cell Responses to Influenza Vaccine

Kang

Hong

Nolasco

et al. 2004

The Journal of Immunology

183

113

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We investigated the relationship of memory CD4+ T cells with the evolution of influenza virus-specific CD4+ T cell responses in healthy young and elderly people. Elderly individuals had a similar frequency of CD69+CD4+ T cells producing IFN-γ and TNF-α at 1 wk, but a lower frequency of these CD4+ T cells at 3 mo after influenza vaccination. Although the elderly had a higher frequency of central memory (CM; CCR7+CD45RA−) CD4+ T cells, they had a significantly lower frequency of effector memory (EM; CCR7−CD45RA−) CD4+ T cells, and the frequency of the latter memory CD4+ T cells positively correlated with the frequency of influenza virus-specific CD69+CD4+ T cells producing IFN-γ at 3 mo. These findings indicate that the elderly have an altered balance of memory CD4+ T cells, which potentially affects long term CD4+ T cell responses to the influenza vaccine. Compared with the young, the elderly had decreased serum IL-7 levels that positively correlated with the frequency of EM cells, which suggests a relation between IL-7 and decreased EM cells. Thus, although the healthy elderly mount a level of CD4+ T cell responses after vaccination comparable to that observed in younger individuals, they fail to maintain or expand these responses. This failure probably stems from the alteration in the frequency of CM and EM CD4+ T cells in the elderly that is related to alteration in IL-7 levels. These findings raise an important clinical question about whether the vaccination strategy in the elderly should be modified to improve cellular immune responses.

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Section: Discussionmentioning

confidence: 65%

Age-Associated Change in the Frequency of Memory CD4+ T Cells Impairs Long Term CD4+ T Cell Responses to Influenza Vaccine

Kang

Hong

Nolasco

et al. 2004

The Journal of Immunology

183

113

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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.…”

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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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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“…However, it was recently reported that inducing the resting T-cells to enter into the G 1b phase of the cell cycle by stimulation through the T-cell receptor and CD28 co-stimulation receptor, using anti-CD3 plus anti-CD28 antibodies, was sufficient to render the cells susceptible to HIV-1 infection and replication [130]. Moreover, exposing T-cells to cytokines that do not trigger cell division could render them permissive to transduction with HIV-1-vectors [134][135][136]. These findings suggest that partial activation of resting T-cells is sufficient for gene transfer by HIV-1-derived vectors and that DNA synthesis or mitosis of these cells is not necessary.…”

Section: Targeting By Specific Vector-mediated Target Cell Activationmentioning

confidence: 99%

Surface-engineering of lentiviral vectors

Verhoeyen

Cosset

2004

J. Gene Med.

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SummaryVectors derived from retroviridae offer particularly flexible properties in gene transfer applications given the numerous possible associations of various viral surface glycoproteins (determining cell tropism) with different types of retroviral cores (determining genome replication and integration). Lentiviral vectors should be preferred gene delivery vehicles over vectors derived from onco-retroviruses such as murine leukemia viruses (MLVs) that cannot transduce non-proliferating target cells. Generating lentiviral vectors pseudotyped with different viral glycoproteins (GPs) may modulate the physicochemical properties of the vectors, their interaction with the host immune system and their host range. There are however important gene transfer restrictions to some non-proliferative tissues or cell types and recent studies have shown that progenitor hematopoietic stem cells in G 0 , nonactivated primary blood lymphocytes or monocytes were not transducible by lentiviral vectors. Moreover, lentiviral vectors that have the capacity to deliver transgenes into specific tissues are expected to be of great value for various gene transfer applications in vivo. Several innovative approaches have been explored to overcome such problems that have given rise to novel concepts in the field and have provided promising results in preliminary evaluations in vivo. Here we review the different approaches explored to upgrade lentiviral vectors, aiming at developing vectors suitable for in vivo gene delivery.

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IL-7 differentially regulates cell cycle progression and HIV-1-based vector infection in neonatal and adult CD4⁺T cells

Cited by 93 publications

References 49 publications

Age-Associated Change in the Frequency of Memory CD4+ T Cells Impairs Long Term CD4+ T Cell Responses to Influenza Vaccine

Age-Associated Change in the Frequency of Memory CD4+ T Cells Impairs Long Term CD4+ T Cell Responses to Influenza Vaccine

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

Surface-engineering of lentiviral vectors

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IL-7 differentially regulates cell cycle progression and HIV-1-based vector infection in neonatal and adult CD4+T cells

Cited by 93 publications

References 49 publications

Age-Associated Change in the Frequency of Memory CD4+ T Cells Impairs Long Term CD4+ T Cell Responses to Influenza Vaccine

Age-Associated Change in the Frequency of Memory CD4+ T Cells Impairs Long Term CD4+ T Cell Responses to Influenza Vaccine

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

Surface-engineering of lentiviral vectors

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Product

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About

IL-7 differentially regulates cell cycle progression and HIV-1-based vector infection in neonatal and adult CD4⁺T cells