The Role of NK Cells in the Control of Viral Infection in HTLV-1 Carriers.

Camila F Amorim,Natália B Carvalho,José Abraão Neto,Silvane B Santos,Edgar M Carvalho,Maria Fernanda Rios Grassi,Lucas P Carvalho

doi:10.1155/2019/6574828

Abstract

The cytotoxic activities of CD8+ T cells have been considered the main defense mechanism against the human T lymphotropic virus type 1 (HTLV-1). As with CD8+ T cells, NK cells can perform cytotoxic degranulation with production of cytotoxic mediators, such as perforins and granzymes. NK cells are also responsible for antibody-dependent cellular cytotoxicity (ADCC) against infected cells, but few studies have evaluated the role of NK cells in HTLV-1 infection. The aim of this study was to characterize the subsets and measure the frequency of NK cells in HTLV-1 carriers (HC) and in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and correlate these findings with the proviral load and development of HAM/TSP. The diagnosis of HTLV-1 infection was performed with a detection antibody against viral antigens by ELISA and confirmed by Western blot. Phenotypic characterization of NK cells was performed by flow cytometry. The frequencies of CD56+, CD56+CD3−, CD56+CD16+, and CD56dim cells were decreased in HAM/TSP patients. The frequency of CD56+CD3− cells was inversely correlated with proviral load in HC but not in HAM/TSP patients. HAM/TSP patients showed decreased frequency of CD56+ and CD56dim cells expressing CD16, the main receptor for ADCC. These data indicate that NK cells may play a key role in the control of HTLV-1 infection by preventing the progression of HC to HAM/TSP.

Highlights

The immune response against viral infection is based on effector mechanisms from both the innate and adaptive immune response
In human T lymphotropic virus type 1 (HTLV-1) infection, while NK cells seek to limit the replication of the virus-infected cells and proviral load in the early stages of infection, the CTLs are responsible for the control of viral latency [1]
The HTLV-1 carriers (HC) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients were significantly older than seronegative individuals (SN), but there was no difference regarding age between the HTLV-1 positive groups

Summary

Introduction

The immune response against viral infection is based on effector mechanisms from both the innate and adaptive immune response Among these mechanisms, the cytotoxicity mediated by NK cells and cytotoxic CD8+ T cells (CTL) is responsible for killing infected cells. NK cells as well as CTLs have the ability to directly kill infected cells through the production of perforins and granzymes in cytotoxic granules These granules are released from cytotoxic cells surrounded initially by a lipid bilayer containing lysosomal membrane glycoproteins, including CD107a. Over the past 15 years, a “new” population of cells expressing both CD3 and CD56 and called NKT cells has been described [5] Half of these cells express CD16 and all of them express classical T cell receptors (TCRs) that

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