학술논문

Enhanced T-Cell Maturation and Monocyte Aggregation Are Features of Cellular Inflammation in Human T-Lymphotropic Virus Type 1–Associated Myelopathy.
Document Type
Article
Source
Clinical Infectious Diseases. Apr2020, Vol. 70 Issue 7, p1326-1335. 10p.
Subject
*BIOMARKERS
*CELL physiology
*CELLULITIS
*EXTRACELLULAR space
*FLOW cytometry
*HIV
*IMMUNOSUPPRESSION
*MONOCYTES
*NUCLEIC acids
*MYELITIS
*T cells
*CD4 antigen
Language
ISSN
1058-4838
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 (CD28null) 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 FROM AUTHOR]