Characterization of a Novel Population of Low-Density Granulocytes Associated with Disease Severity in HIV-1 Infection

Thomas Cloke,Ingrid Müller,Graham Taylor,Markus Munder,Pascale Kropf,Adriano Boasso

doi:10.1371/journal.pone.0048939

Abstract

The mechanisms resulting in progressive immune dysfunction during the chronic phase of HIV infection are not fully understood. We have previously shown that arginase, an enzyme with potent immunosuppressive properties, is increased in HIV seropositive (HIV+) patients with low CD4+ T cell counts. Here we show that the cells expressing arginase in peripheral blood mononuclear cells of HIV+ patients are low-density granulocytes (LDGs) and that whereas these cells have a similar morphology to normal-density granulocyte, they are phenotypically different. Importantly, our results reveal that increased frequencies of LDGs correlate with disease severity in HIV+ patients.

Highlights

Since the initial report of AIDS in 1981, approximately 60 million people have become infected with HIV of which more than 30 million have died
We have previously shown that arginase activity is higher in peripheral blood mononuclear cells (PBMCs) isolated from HIV-1 infected individuals with low CD4+ T cell counts and that this coincided with lower levels of L-arginine [12]
We have previously shown that arginase activity is significantly higher in PBMCs of HIV+ individuals with low CD4+ T cell counts

Summary

Introduction

Since the initial report of AIDS in 1981, approximately 60 million people have become infected with HIV of which more than 30 million have died. Depletion of CD4+ T cells explains much of the immune suppression in HIV infected individuals, the precise reasons for the onset of immunopathology during HIV infection are not yet fully understood [1,2,3,4]. An enzyme of the urea cycle, can be expressed in cells of the immune system and has been shown to exert potent immunoregulatory functions: a reduction in the bioavailability of L-arginine by arginase results in impaired T cell responses, characterized by down-regulation of T cell proliferation, reduced expression of CD3f and cytokine production [5,6,7,8]. We have previously shown that arginase activity is higher in peripheral blood mononuclear cells (PBMCs) isolated from HIV-1 infected individuals with low CD4+ T cell counts and that this coincided with lower levels of L-arginine [12]. We characterized the phenotype of arginase-expressing cells in HIV+ patients and tested the hypothesis that their frequency correlated with markers of disease severity

Methods

Results

Conclusion