IL-7 and IL-15: therapeutic cytokines for immunodeficiency

Alpdoğan, Önder; Brink, Marcel R.M. van den

doi:10.1016/j.it.2004.11.002

Cited by 142 publications

(119 citation statements)

References 94 publications

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“…IL-15 is produced in the skin by monocytes, macrophages, and keratinocytes and plays an important role in functional maturation of APCs and induction of a Th1-type response (20). IL-15 mRNA expression was limited during the initial 8 h of inflammatory response in all skin samples (Fig.…”

Section: Up-regulation Of Th1-associated Cytokines In Spr ϩ Specimensmentioning

confidence: 96%

Characterization of the Divergent Wound-Healing Responses Occurring in the Pathergy Reaction and Normal Healthy Volunteers

Melikoğlu

Uysal

Krueger³

et al. 2006

The Journal of Immunology

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Behçet’s disease (BD) is a multisystem inflammatory disorder of unknown etiology characterized by recurrent oral and genital ulcerations and uveitis, with varying other manifestations associated with vascular inflammation. A unifying feature of BD inflammation is the skin pathergy reaction (SPR), a nonspecific tissue hyperreactivity to minor trauma involving epithelial disruption. This study compared skin responses to needle prick in BD patients and normal healthy volunteers. Two study groups, each consisting of 10 BD patients with SPR+ and 6 controls, were evaluated using either immunohistochemistry or quantitative real-time PCR to measure inflammatory cell and cytokine levels in biopsy specimens obtained serially from independent sites at 0, 8, and 48 h after needle prick. We found similar cellular infiltration patterns in response to needle prick in BD patients and controls between 0 and 8 h. Further development of this immune response was limited in skin of normal control subjects, with stable or decreased inflammatory mediators observed at 48 h. In contrast, in BD-derived skin specimens, increased influxes of mature dendritic cells, monocytes, and lymphocytes, including T regulatory cells, were noted by 48 h. Similarly, increases in cytokines (IFN-γ, IL-12 p40, IL-15), chemokines (MIP3-α, IP-10, Mig, and iTac), and adhesion molecules (ICAM-1, VCAM-1) were noted at 48 h in the skin of BD patients with SPR+ but not in the skin of normal controls. These results suggest that, in contrast to the self-limited inflammation associated with epithelial disruption of normal skin, BD patients experience marked cellular influxes into the injury site, leading to an exaggerated lymphoid Th1-type response.

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Section: Up-regulation Of Th1-associated Cytokines In Spr ϩ Specimensmentioning

confidence: 96%

Characterization of the Divergent Wound-Healing Responses Occurring in the Pathergy Reaction and Normal Healthy Volunteers

Melikoğlu

Uysal

Krueger³

et al. 2006

The Journal of Immunology

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“…For example, IL-7 is an essential cytokine for T-lymphocyte development, survival, expansion, and maturation in humans. Phase I clinical trials in cancer patients and HIV-infected patients have shown that T-cell expansion can be achieved at doses that are well tolerated (193,194). The use of ligands of co-activator receptors for effector T lymphocytes may also have beneficial effects.…”

Section: Future Therapeutic Strategies and Conclusionmentioning

confidence: 99%

Monitoring Immune Dysfunctions in the Septic Patient: A New Skin for the Old Ceremony

Monneret

Venet

Pachot

et al. 2008

Mol Med

302

323

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“…Cytokines such as IL-7 and IL-15 increase T cell proliferation and function and constitute attractive therapeutic platforms for the treatment of HIV-1 infection (11). Both IL-7 and IL-15 regulate the generation and maintenance of memory CD4 ϩ and CD8 ϩ T cells following exposure to Ag (12)(13)(14)(15)(16).…”

Section: H Uman Immunodeficiency Virus Infection Of Humans Ifmentioning

confidence: 99%

Interleukin-15 but Not Interleukin-7 Abrogates Vaccine-Induced Decrease in Virus Level in Simian Immunodeficiency Virusmac251-Infected Macaques

Hryniewicz

Price

Moniuszko

et al. 2007

The Journal of Immunology

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The loss of CD4+ T cells and the impairment of CD8+ T cell function in HIV infection suggest that pharmacological treatment with IL-7 and IL-15, cytokines that increase the homeostatic proliferation of T cells and improve effector function, may be beneficial. However, these cytokines could also have a detrimental effect in HIV-1-infected individuals, because both cytokines increase HIV replication in vitro. We assessed the impact of IL-7 and IL-15 treatment on viral replication and the immunogenicity of live poxvirus vaccines in SIVmac251-infected macaques (Macaca mulatta). Neither cytokine augmented the frequency of vaccine-expanded CD4+ or CD8+ memory T cells, clonal recruitment to the SIV-specific CD8+ T cell pool, or CD8+ T cell function. Vaccination alone transiently decreased the viral set point following antiretroviral therapy suspension. IL-15 induced massive proliferation of CD4+ effector T cells and abrogated the ability of vaccination to decrease set point viremia. In contrast, IL-7 neither augmented nor decreased the vaccine effect and was associated with a decrease in TGF-β expression. These results underscore the importance of testing immunomodulatory approaches in vivo to assess potential risks and benefits for HIV-1-infected individuals.

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IL-7 and IL-15: therapeutic cytokines for immunodeficiency

Cited by 142 publications

References 94 publications

Characterization of the Divergent Wound-Healing Responses Occurring in the Pathergy Reaction and Normal Healthy Volunteers

Characterization of the Divergent Wound-Healing Responses Occurring in the Pathergy Reaction and Normal Healthy Volunteers

Monitoring Immune Dysfunctions in the Septic Patient: A New Skin for the Old Ceremony

Interleukin-15 but Not Interleukin-7 Abrogates Vaccine-Induced Decrease in Virus Level in Simian Immunodeficiency Virusmac251-Infected Macaques

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