Enhanced T-cell maturation and monocyte aggregation are features of cellular inflammation in human T-lymphotropic virus type-1-associated myelopathy
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Author(s)
Saeed, zainab
Rowan, aileen
Greiller, claire
Taylor, graham
Pollock, Katrina
Type
Journal Article
Abstract
Background
Human T-lymphotropic virus type-1 (HTLV-1) associated myelopathy (HAM), is an inflammatory condition characterised by severe disability and high levels of infected white blood cells. The circulating cellular inflammatory changes that distinguish this condition from asymptomatic infection are not well understood.
Methods
To investigate the immune characteristics of individuals with low or high HTLV-1 proviral load (pVL), symptomatic disease and the impact of immunosuppressive therapy, thirty-eight women living with HTLV-1 infection, with a median age 59 (52-68) years were studied. Nineteen were asymptomatic carriers, with low or high pVL, and nineteen were diagnosed with HAM, with ten receiving anti-inflammatory therapy. Peripheral blood mononuclear cells were stained and analysed for frequency distribution and activation of innate and adaptive immune cell subsets using multi-parameter flow cytometry.
Results
Inflation of the CD4:CD8 ratio (>2) was observed amongst all groups irrespective of pVL. The frequency of naïve CD4+ T-cells correlated inversely with HTLV-1 pVL (rs=-0.344, p=0.026). Mature TEM CD4+ T-cells were expanded in patients with untreated HAM compared with asymptomatic carriers (p<0.001), but less so in those on therapy. High levels of exhausted (PD-1+) and senescent (CD28null) CD4+ and CD8+ T-cells were observed in all individuals particularly in those with HAM, whilst monocytes showed increased aggregation, and CD14+CD56- monocytes were less frequent.
Conclusions
CD4:CD8 ratio inflation is a feature of HTLV-1 infection, whereas enhanced CD4+ T-cell maturation and monocyte aggregation are features of HAM reflecting widespread inflammatory change, which may be detectable pre-symptomatically, and be amenable to anti-inflammatory treatment.
Human T-lymphotropic virus type-1 (HTLV-1) associated myelopathy (HAM), is an inflammatory condition characterised by severe disability and high levels of infected white blood cells. The circulating cellular inflammatory changes that distinguish this condition from asymptomatic infection are not well understood.
Methods
To investigate the immune characteristics of individuals with low or high HTLV-1 proviral load (pVL), symptomatic disease and the impact of immunosuppressive therapy, thirty-eight women living with HTLV-1 infection, with a median age 59 (52-68) years were studied. Nineteen were asymptomatic carriers, with low or high pVL, and nineteen were diagnosed with HAM, with ten receiving anti-inflammatory therapy. Peripheral blood mononuclear cells were stained and analysed for frequency distribution and activation of innate and adaptive immune cell subsets using multi-parameter flow cytometry.
Results
Inflation of the CD4:CD8 ratio (>2) was observed amongst all groups irrespective of pVL. The frequency of naïve CD4+ T-cells correlated inversely with HTLV-1 pVL (rs=-0.344, p=0.026). Mature TEM CD4+ T-cells were expanded in patients with untreated HAM compared with asymptomatic carriers (p<0.001), but less so in those on therapy. High levels of exhausted (PD-1+) and senescent (CD28null) CD4+ and CD8+ T-cells were observed in all individuals particularly in those with HAM, whilst monocytes showed increased aggregation, and CD14+CD56- monocytes were less frequent.
Conclusions
CD4:CD8 ratio inflation is a feature of HTLV-1 infection, whereas enhanced CD4+ T-cell maturation and monocyte aggregation are features of HAM reflecting widespread inflammatory change, which may be detectable pre-symptomatically, and be amenable to anti-inflammatory treatment.
Date Issued
2020-04-01
Date Acceptance
2019-04-30
Citation
Clinical Infectious Diseases, 2020, 70 (7), pp.1326-1335
ISSN
1058-4838
Publisher
Oxford University Press (OUP)
Start Page
1326
End Page
1335
Journal / Book Title
Clinical Infectious Diseases
Volume
70
Issue
7
Copyright Statement
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.This is an Open Access article distributedunder the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Subjects
HAM/TSP
HTLV-1
HTLV-1–associated myelopathy
cellular maturation
inflammation
06 Biological Sciences
11 Medical and Health Sciences
Microbiology
Publication Status
Published
Date Publish Online
2019-05-07