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Clin Infect Dis. 2019 May 7. pii: ciz369. doi: 10.1093/cid/ciz369. [Epub ahead of print]

Enhanced T-cell maturation and monocyte aggregation are features of cellular inflammation in human T-lymphotropic virus type-1-associated myelopathy.

Author information

1
Section of Virology, Department of Medicine, Imperial College London, London, UK.

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.

KEYWORDS:

HAM/TSP; HTLV-1; HTLV-1 associated myelopathy; cellular maturation; inflammation

PMID:
31063543
DOI:
10.1093/cid/ciz369

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