Cytokines and Cell Surface Molecules Independently Induce CXCR4 Expression on CD4+ CCR7+ Human Memory T Cells

Jourdan, Patrick; Vendrell, Jean-Pierre; Huguet, Marie-France; Segondy, Michel; Bousquet, Jean; Pène, Jérôme; Yssel, Hans

doi:10.4049/jimmunol.165.2.716

Cited by 106 publications

(87 citation statements)

References 45 publications

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“…18,40 -42 In further support are studies indicating that Th1-type lymphocytes have very little or no expression of CxCR4, whereas Th2-type lymphocytes express CxCR4 on their surface. 20,41 In agreement with our data is a recent study that indicates that SDF-1 and CxCR4 are directly involved in the asthmatic response in an ovalbumin model of asthma. 21 Thus, the role of CxCR4 during an allergic/asthmatic pulmonary response may reflect the altered immune environment leading to increased lung damage and airway reactivity.…”

Section: Discussionsupporting

confidence: 93%

AMD3100, a CxCR4 Antagonist, Attenuates Allergic Lung Inflammation and Airway Hyperreactivity

Lukacs

Berlin

Schols

et al. 2002

The American Journal of Pathology

195

149

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The role of specific chemokine receptors during allergic asthmatic responses has been relatively undefined. A number of receptors are preferentially expressed on Th2 cells, including CCR4, CCR8, and CxCR4. In the present study, we have examined the role of CxCR4 in the development of cockroach allergen-induced inflammation and airway hyperreactivity in a mouse model of asthma. Using a specific inhibitor of CxCR4, AMD3100, our results indicate that blocking this receptor has a significant effect in down-regulating the inflammation and pathophysiology of the allergen-induced response. Treatment of allergic mice with AMD3100 significantly reduced airway hyperreactivity, peribronchial eosinophilia, and the overall inflammatory responses. In addition, there was a shift in the cytokine profile that was observed in the AMD3100-treated animals. Specifically, there was a significant reduction in interleukin-4 and interleukin-5 levels and a significant increase in interleukin-12 and interferon-␥ levels within the lungs of treated allergic mice. Furthermore, there was a significant alteration in the local chemokine production of CCL22 (MDC) and CCL17 (TARC), two chemokines previously shown to be important in Th2-type allergen responses. Overall, specifically blocking CxCR4 using AMD3100 reduced a number of pathological parameters related to asthmatic-type inflammation.

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Section: Discussionsupporting

confidence: 93%

AMD3100, a CxCR4 Antagonist, Attenuates Allergic Lung Inflammation and Airway Hyperreactivity

Lukacs

Berlin

Schols

et al. 2002

The American Journal of Pathology

195

149

View full text Add to dashboard Cite

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“…This result contrasts with other studies that describe down-regulation of CXCR4 and CCR5 by IFN-␣ in PBMCs or cell lines and macrophages derived from CD34 ϩ cells from umbilical cord blood, respectively (69,70). Conversely, IL-7 up-regulated CXCR4 expression in T cells, PBMCs, and thymocytes, and this effect was associated with increased susceptibility to infection with X4 HIV strains (28,30,32,37). The disparate results from these and our experiments may be explained by the different experimental systems used.…”

Section: Discussioncontrasting

confidence: 91%

“…Pharmacological doses induce a central renewal and a peripheral expansion of CD4 ϩ and CD8 ϩ T cells in macaques infected with SIV (23,24). However, in vitro, IL-7 enhances HIV replication (2,3,(25)(26)(27)(28)(29)(30)(31)(32). Its effects on HIV replication in SCID-hu mice or SIV-infected monkeys have been inconsistent (23,24,33,34), and IL- 7 has not yet been tested in clinical trials of HIV therapy.…”

mentioning

confidence: 99%

Uncoupled Anti-HIV and Immune-Enhancing Effects when Combining IFN-α and IL-7

Audigé¹,

Schlaepfer²,

Joller

et al. 2005

The Journal of Immunology

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Cytokine-based therapies have been examined for purging viral reservoirs and immunomodulation in HIV infection. However, single cytokines did not result in either HIV eradication or an efficient HIV-specific immune response. We hypothesize that cytokines with distinct biologic effects need to be combined for immunotherapy of HIV infection. In this study, we investigated the anti-HIV activity and immune-enhancing effects of the combination of IFN-α and IL-7. In human lymphocyte aggregate cultures infected ex vivo with the X4 HIV strain NL4-3, IFN-α/IL-7 potently inhibited HIV replication and preserved CD4+ T cells, probably by up-regulating Bcl-2. IFN-α/IL-7 also strongly inhibited R5 HIV replication. Furthermore, in allogeneic MLRs, IFN-α/IL-7 increased T cell proliferation and IFN-γ production. IFN-α alone also had strong anti-HIV activity, but neither preserved CD4+ T cells nor increased T cell responses in MLRs. IL-7 alone maintained T cells and enhanced T cell activation in MLRs, but only moderately inhibited or increased HIV replication. Thus, coadministration of IFN-α/IL-7 combines the potent anti-HIV activity of IFN-α with the beneficial effects of IL-7 on T cell survival and function. We speculate that IFN-α will block viral replication, activate APCs, and up-regulate MHC molecules, thus allowing IL-7 to display its effects for generating an efficient immune response. In this scenario, the known reactivation of latent HIV by IL-7 may be advantageous.

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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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Cytokines and Cell Surface Molecules Independently Induce CXCR4 Expression on CD4+ CCR7+ Human Memory T Cells

Cited by 106 publications

References 45 publications

AMD3100, a CxCR4 Antagonist, Attenuates Allergic Lung Inflammation and Airway Hyperreactivity

AMD3100, a CxCR4 Antagonist, Attenuates Allergic Lung Inflammation and Airway Hyperreactivity

Uncoupled Anti-HIV and Immune-Enhancing Effects when Combining IFN-α and IL-7

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

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