Enhanced T-Cell Maturation and Monocyte Aggregation Are Features of Cellular Inflammation in Human T-Lymphotropic Virus Type 1–Associated Myelopathy. (7th May 2019)

• Record Type: Journal Article
• Authors: Saeed, Zainab; Rowan, Aileen; Greiller, Claire; Taylor, Graham P; Pollock, Katrina M
• Is Part Of: Clinical infectious diseases. Volume 70:Number 7(2020)
• Page Start: 1326
• Page End: 1335
• Publication Date: 2019-05-07
• Subjects: HTLV-1 -- HAM/TSP -- HTLV-1–associated myelopathy -- inflammation -- cellular maturation; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciz369
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: Human T-lymphotropic virus type 1 (HTLV-1)–associated myelopathy (HAM) is an inflammatory condition characterized 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, 38 women living with HTLV-1 infection, at a median age of 59 (52–68) years, were studied. Nineteen were asymptomatic carriers with low or high pVL; 19 were diagnosed with HAM, with 10 receiving anti-inflammatory therapy. Peripheral blood mononuclear cells were stained and analyzed for frequency distribution and activation of innate and adaptive immune cell subsets using multiparameter flow cytometry. Results: Inflation of the CD4:CD8 ratio (>2) was observed among all groups irrespective of pVL. The frequency of naive CD4 + T cells correlated inversely with HTLV-1 pVL (rs = –0.344, P = .026). Mature T effector memory TEM CD4 + T cells were expanded in patients with untreated HAM compared with asymptomatic carriers ( P < .001) but less so in those on therapy. High levels of exhausted (PD-1 + ) and senescent (CD28 null ) CD4 + and CD8 + T cells were observed in all individuals, particularly in those with HAM, while 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 presymptomatically and be amenable to anti-inflammatory treatment. Abstract : Human T-lymphotropic virus type 1–associated myelopathy (HAM) occurs during chronic infection with high proviral burden. We show widespread cellular inflammatory changes in HAM patients that could be partially ameliorated with anti-inflammatory treatment and are potential biomarkers to guide treatment initiation.