IL-7 and CD4+ T-cell proliferation

Jaleco, Sara; Kinet, Sandrina; Hassan, Jaythoon; Dardalhon, Valérie; Swainson, Louise; Reen, Denis J.; Taylor, Naomi

doi:10.1182/blood-2002-06-1760

Cited by 8 publications

(8 citation statements)

References 26 publications

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“…The fact that the kinetics of HLA-DR ϩ cells correlates with that of Ki67 ϩ cells strongly suggests that these activated cells, mostly memory cells, are those that are able to proliferate in the presence of IL-7. These data are in agreement with the study of Jaleco et al (30) who showed that under conditions where the HLA-DR ϩ cells are removed, purified human CD4 ϩ T cells fail to proliferate in response to IL-7. Several ex vivo studies in humans also indicate that IL-7 does not promote the proliferation of naive T cells (32)(33)(34) except in the case of the immature naive cells of the human cord blood which have been identified as recent thymic emigrants (33,35).…”

Section: Discussionsupporting

confidence: 93%

“…It has been recently shown that the human CD4 ϩ T lymphocytes expressing the HLA-DR activation marker specifically proliferate in the presence of rhIL-7 in vitro (30). We thus wondered whether rhIL-7 might up-regulate in vivo this activation marker and whether this activation correlates with the capacity to proliferate, as characterized by the expression of the Ki67 marker.…”

Section: Rhil-7 Increases T Cell Activation and Proliferationmentioning

confidence: 99%

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IL-7 Stimulates T Cell Renewal Without Increasing Viral Replication in Simian Immunodeficiency Virus-Infected Macaques

Nugeyre

Monceaux

Beq

et al. 2003

The Journal of Immunology

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The main failure of antiretroviral therapy is the lack of restoration of HIV-specific CD4+ T cells. IL-7, which has been shown to be a crucial cytokine for thymopoiesis, has been envisaged as an additive therapeutic strategy. However, in vitro studies suggest that IL-7 might sustain HIV replication in thymocytes and T lymphocytes. Therefore, in the present study, we evaluated the effect of IL-7 on both T cell renewal and viral load in SIVmac-infected young macaques in the absence of antiretroviral therapy. This evaluation was conducted during the asymptomatic phase in view of a potential treatment of HIV patients. We show that IL-7 induces both a central renewal and a peripheral expansion of T lymphocytes associated with cell activation. No alarming modulation of the other hemopoietic cells was observed. No increase in the viral load was shown in blood or lymph nodes. These data strengthen the rationale for the use of IL-7 as an efficient immunotherapy in AIDS.

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Section: Discussionsupporting

confidence: 93%

Section: Rhil-7 Increases T Cell Activation and Proliferationmentioning

confidence: 99%

IL-7 Stimulates T Cell Renewal Without Increasing Viral Replication in Simian Immunodeficiency Virus-Infected Macaques

Nugeyre

Monceaux

Beq

et al. 2003

The Journal of Immunology

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“…These IL-7-responding cells expressed HLA-DR. RTE are activated in the thymus. Mature precursor T cells are activated by cytokines such as TNF and IL-7 before leaving the thymic microenvironment (41). Mature thymocytes have been shown to contain activated NF-B and the activation marker HLA-DR.…”

Section: Discussionmentioning

confidence: 99%

IL-7 Induces Immunological Improvement in SIV-Infected Rhesus Macaques under Antiviral Therapy

Beq

Nugeyre

Fang

et al. 2006

The Journal of Immunology

102

103

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Despite efficient antiretroviral therapy (ART), CD4+ T cell counts often remain low in HIV-1-infected patients. This has led to IL-7, a crucial cytokine involved in both thymopoiesis and peripheral T cell homeostasis, being suggested as an additional therapeutic strategy. We investigated whether recombinant simian IL-7-treatment enhanced the T cell renewal initiated by ART in rhesus macaques chronically infected with SIVmac251. Six macaques in the early chronic phase of SIV infection received antiretroviral treatment. Four macaques also received a 3-wk course of IL-7 injections. Viral load was unaffected by IL-7 treatment. IL-7 treatment increased the number of circulating CD4+ and CD8+ memory T cells expressing activation (HLA-DR+, CD25+) and proliferation (Ki-67+) markers. It also increased naive (CD45RAbrightCD62L+) T cell counts by peripheral proliferation and enhanced de novo thymic production. The studied parameters returned to pretreatment values by day 29 after the initiation of treatment, concomitantly to the appearance of anti-IL-7 neutralizing Abs, supporting the need for a nonimmunogenic molecule for human treatment. Thus, IL-7, which increases T cell memory and de novo renewal of naive T cells may have additional benefits in HIV-infected patients receiving ART.

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“…19 These findings were in contrast to the idea that resting T cells do not support active HIV replication unless they are stimulated to pass beyond the G1b phase of the cell cycle. [20][21][22] Others have demonstrated that resting naïve T cells in lymphoid tissue can support HIV replication without passing through the G1b phase of the cell cycle, suggesting that the environmental milieu may have an impact on HIV infection. 23 We believe that IL-7 is a key factor that may regulate HIV infection of naïve T cells.…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐7 signalling is sufficient to phenotypically and functionally prime human CD4⁺ naïve T cells

2005

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Summary Interleukin‐7 (IL‐7) is produced by bone marrow and lymphoid stromal cells and is involved in the synthesis, survival and homeostasis of T cells. These attributes are the basis for current strategies to utilize IL‐7 as an immune modulator for several clinical conditions to replenish depleted T‐cell numbers. Because we had previously determined that IL‐7 can induce potent human immunodeficiency virus replication in the otherwise non‐permissive CD4+ naïve T‐cell compartment, we evaluated here the impact of IL‐7 on the phenotype and functional potential of naïve CD4+ T cells in an attempt to understand the mechanism of this induction. We demonstrate that IL‐7 mediated the up‐regulation of CD25, CD95 and human leucocyte antigen‐DR, while it did not alter the expression of CD45RO, CD69, CD40, or CD154. Examination of the cytokine profile of IL‐7‐treated naïve T cells using a Type1/Type2 Proteome Array indicated a remarkable IL‐7‐mediated induction of interferon‐γ production, while the other cytokines evaluated (IL‐2, IL‐12, tumour necrosis factor‐α, IL‐4, IL‐5, IL‐10 and IL‐13) were not affected. Intracellular staining of IL‐7‐treated naïve T cells for interferon‐γ verified the Proteome data. IL‐7 did not induce cell cycle proliferation of naïve CD4+ T cells, as evaluated by 7‐AAD/pyronin immunostaining and carboxyfluorescein diacetate succinimidyl ester dye tracking. IL‐7 treatment of naïve CD4+ T cells induced their ability to prime monocytes, as was indicated by induction of CD80 and CD86 expression on monocytes cocultured with IL‐7‐treated naïve CD4+ T cells. Collectively, these data indicate that IL‐7 signalling is sufficient to phenotypically and functionally prime human CD4+ naïve T cells independent of antigen stimulation.

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IL-7 and CD4+ T-cell proliferation

Cited by 8 publications

References 26 publications

IL-7 Stimulates T Cell Renewal Without Increasing Viral Replication in Simian Immunodeficiency Virus-Infected Macaques

IL-7 Stimulates T Cell Renewal Without Increasing Viral Replication in Simian Immunodeficiency Virus-Infected Macaques

IL-7 Induces Immunological Improvement in SIV-Infected Rhesus Macaques under Antiviral Therapy

Interleukin‐7 signalling is sufficient to phenotypically and functionally prime human CD4⁺ naïve T cells

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IL-7 and CD4+ T-cell proliferation

Cited by 8 publications

References 26 publications

IL-7 Stimulates T Cell Renewal Without Increasing Viral Replication in Simian Immunodeficiency Virus-Infected Macaques

IL-7 Stimulates T Cell Renewal Without Increasing Viral Replication in Simian Immunodeficiency Virus-Infected Macaques

IL-7 Induces Immunological Improvement in SIV-Infected Rhesus Macaques under Antiviral Therapy

Interleukin‐7 signalling is sufficient to phenotypically and functionally prime human CD4+ naïve T cells

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Interleukin‐7 signalling is sufficient to phenotypically and functionally prime human CD4⁺ naïve T cells