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

Abstract

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.

Interleukin 7 reduces the levels of spontaneous apoptosis in CD4+and CD8+T cells from HIV-1-infected individuals

“…Studies of IL-7 administration to uninfected and SIV-infected macaques have demonstrated a proliferative effect on CD4 ϩ and CD8 ϩ T cells expressing both memory and naïve phenotypes (27,28,38). Analogous results were obtained more recently in human cancer patients (39), as well as in HIV-1-infected individuals (M. Lederman, personal communication).…”

“…At doses that promote T cell proliferation, IL-7 has been reported to induce the transcription of latent HIV-1 in resting peripheral blood CD4 ϩ T cells derived from infected patients on antiretroviral therapy cultured for several weeks ex vivo (26). However, in vivo administration of IL-7 to SIVinfected macaques did not cause a detectable increase in viral load both in lymph nodes and in peripheral blood, despite a widespread induction of T cell proliferation (27,28).…”

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

“…Both IL-7 and IL-15 are cytokines produced by stromal cells that directly affect the homeostatic proliferation of memory T cells and regulate effector function (63,64). Prior studies on naive or SIV-infected macaques treated with rIL-7 protein have demonstrated that this cytokine alters T cell homeostasis (27,28,65) without altering SIV replication (66). The use of rIL-15 has been pioneered in naive macaques alone or together with Ags (26) and has been demonstrated to increase the frequency of long-lived CD4 ϩ and CD8 ϩ T cells.…”

To kill or be killed: how HIV exhausts the immune system

“…153 In macaques infected with SIV, IL-7 induces both central renewal and a peripheral expansion of T lymphocytes associated with cell activation, without increasing the viral load. 154 However, comparison of pathogenic and nonpathogenic models of SIV infection showed that elevated levels of IL-7 are associated with disease progression. 155 Similarly, in HIV-infected subjects, falling CD4 þ T-cell counts are associated with increased circulating levels of IL-7.…”