Functional capacity of natural killer cells in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients

Gabriel Andrade Nonato Queiroz,Maria Fernanda Rios Grassi,Bernardo Galvão-Castro,Vincent Vieillard,Rita Elizabeth Moreira Mascarenhas,Raphaela Lisboa Andrade

doi:10.1186/s12879-019-4032-1

Abstract

BackgroundNatural killer (NK) cells are part of the innate immune system and provide surveillance against viruses and cancers. The ability of NK cells to kill virus-infected cells depends on the balance between the effects of inhibitory and activating NK cell receptors. This study aimed to investigate the phenotypic profile and the functional capacity of NK cells in the context of HTLV-1 infection.MethodsThis cross-sectional study sequentially recruited HTLV-1 infected individuals with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and asymptomatic HTLV-1 (AS) from the Integrated and Multidisciplinary HTLV Center in Salvador, Brazil. Blood samples from healthy blood donors served as controls. NK cell surface receptors (NKG2D, KIR2DL2/KIR2DL3, NKp30, NKG2A, NKp46, TIM-3 and PD-1), intracellular cytolytic (Granzyme B, perforin) and functional markers (CD107a for degranulation, IFN-γ) were assayed by flow cytometry in the presence or absence of standard K562 target cells. In addition, cytotoxicity assays were performed in the presence or absence of anti-NKp30.ResultsThe frequency of NKp30+ NK cells was significantly decreased in HAM/TSP patients [58%, Interquartile Range (IQR) 30–61] compared to controls (73%, IQR 54–79, p = 0.04). The production of cytolytic (perforin, granzyme B) and functional markers (CD107a and IFN-γ) was higher in unstimulated NK cells from HAM/TSP and AS patients compared to controls. By contrast, stimulation with K562 target cells did not alter the frequency of CD107a+ NK cells in HAM/TSP subjects compared to the other groups. Blockage of the NKp30 receptor was shown to decrease cytotoxic activity (CD107a) and IFN-γ expression only in asymptomatic HTLV-1-infected individuals.ConclusionsNK cells from individuals with a diagnosis of HAM/TSP present decreased expression of the activating receptor NKp30, in addition to elevated degranulation activity that remained unaffected after blocking the NKp30 receptor.

Highlights

Natural killer (NK) cells are part of the innate immune system and provide surveillance against viruses and cancers
The median Human T-lymphotropic virus type 1 (HTLV-1) proviral load in the HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) group was significantly higher than the asymptomatic HTLV-1 (AS) group (173,146vs. 10,101copies/106 Peripheral blood mononuclear cells (PBMC), respectively) (p = 0.0001)
Cytotoxic marker and IFN-γ expression by NK cells To determine the functional significance of the present phenotypic findings, we investigated the intracellular expression of IFN-γ by NK cells, as well as the cytotoxic markers perforin, granzyme B and CD107a

Summary

Introduction

Natural killer (NK) cells are part of the innate immune system and provide surveillance against viruses and cancers. Human T-lymphotropic virus type 1 (HTLV-1) has been associated with adult T-cell leukemia/Lymphoma (ATLL) [1], infective dermatitis [2] and other inflammatory diseases [3]. This virus may lead to HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), a progressive inflammatory demyelinating disease affecting. Increased proviral loads and an exacerbated activation of the immune system may be seen in asymptomatic individuals infected with HTLV-1 [11, 12]. The present study aimed to investigate the phenotypic profile of NK cells and to evaluate their functional capacity in the context of HTLV-1 infection, especially in subjects with HAM/TSP

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