Abstract

BackgroundHigh HTLV-1 proviral load (PVL) is mainly found in infected individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However one third of asymptomatic carriers may have high PVL.This study aimed to evaluate the impact of PVL in the activation of T lymphocytes of asymptomatic individuals infected with HTLV-1.MethodsMembrane activation markers (CD25+, CD28+, CD45RO+, CD69+, CD62L+, HLA-DR+), FoxP3+ and intracellular IFN-γ expression were evaluated on both CD4+ and CD8+ T-lymphocytes from asymptomatic carriers with PVL ≥ and < 1% of infected cells, using flow cytometry. HTLV-1 proviral load was determined using real-time PCR.ResultsAsymptomatic carriers with PVL ≥ 1% presented a higher frequency of CD4+CD25+CD45RO+ (13.2% vs. 4%, p = 0.02), CD4+HLA-DR+ (18% vs. 8.3%, p = 0.01) and CD4+IFN-γ+ (4.5%; 1%, p = 0.01) T-cells, than healthy donors. HTLV-1 PVL was directly correlated with the proportion of CD4+CD25+CD45RO+ T-cells (R = 0.7, p = 0.003). Moreover, a significant increase in the proportion of CD4 + FoxP3+ T-cells was observed in HTLV-1-infected individuals, compared to healthy donors.ConclusionHTLV-1 PVL is associated with activation of both CD4+ and CD8+ T-lymphocytes in asymptomatic individuals. Prospective studies should be conducted to evaluate whether asymptomatic individuals with higher PVL and high immune activation are more prone to developing HTLV-1-associated diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-453) contains supplementary material, which is available to authorized users.

Highlights

  • High human T-lymphotropic virus type 1 (HTLV-1) proviral load (PVL) is mainly found in infected individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)

  • To investigate the association between PVL and immune system activation, the present study evaluated the phenotypic profile of CD4+ and CD8+ T-cells in asymptomatic individuals infected with HTLV-1

  • A lower frequency of cells expressing CD28 was observed in HTLV-1-infected individuals with PVL

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Summary

Introduction

High HTLV-1 proviral load (PVL) is mainly found in infected individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Prospective studies should be conducted to evaluate whether asymptomatic individuals with higher PVL and high immune activation are more prone to developing HTLV-1-associated diseases. An estimated 10 to 20 million individuals are currently infected with HTLV-1 worldwide, mostly clustered in Japan, the Caribbean, Africa, and Latin America, with Brazil having the highest number of infected individuals [2] This virus is recognized as the etiologic agent of HTLV-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) [3,4] and adult T-cell. The association with these infectious diseases suggests that HTLV-1 may impair the host immune response, possibly leading to immunosuppression. These individuals often present alterations in regulatory T-cells [16,17]

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