1. In vivo T lymphocyte dynamics in humans and the impact of human T-lymphotropic virus 1 infection
- Author
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Asquith, Becca, Zhang, Yan, Mosley, Angelina J., de Lara, Catherine M., Wallace, Diana L., Worth, Andrew, Kaftantzi, Lambrini, Meekings, Kiran, Griffin, George E., Tanaka, Yuetsu, Tough, David F., Beverley, Peter C., Taylor, Graham P., Macallan, Derek C., and Bangham, Charles R.M.
- Subjects
HTLV-I (Virus) -- Research ,Science and technology - Abstract
Human T-lymphotropic virus type 1 (HTLV-1) is a persistent CD[4.sup.+] T-lymphotropic retrovirus. Most HTLV-1-infected individuals remain asymptomatic, but a proportion develop adult T cell leukemia or inflammatory disease. It is not fully understood how HTLV-1 persists despite a strong immune response or what determines the risk of HTLV-1-associated diseases. Until recently, it has been difficult to quantify lymphocyte kinetics in humans in vivo. Here, we used deuterated glucose labeling to quantify in vivo lymphocyte dynamics in HTLV-1-infected individuals. We then used these results to address four questions. (i) What is the impact of HTLV-1 infection on lymphocyte dynamics? (ii) How does HTLV-1 persist? (iii) What is the extent of HTLV-1 expression in vivo? (iv) What features of lymphocyte kinetics are associated with HTLV-1-associated myelopathy/tropical spastic paraparesis? We found that CD[4.sup.+]CD45R[O.sup.+] and CD[8.sup.+]CD45R[O.sup.+] T lymphocyte proliferation was elevated in HTLV-1-infected subjects compared with controls, with an extra 1012 lymphocytes produced per year in an HTLV-1-infected subject. The in vivo proliferation rate of CD[4.sup.+]CD45R[O.sup.+] cells also correlated with ex vivo viral expression. Finally, the inflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis was associated with significantly increased CD[4.sup.+]CD45R[O.sup.+] cell proliferation. We suggest that there is persistent viral gene expression in vivo, which is necessary for the maintenance of the proviral load and determines HTLV-1-associated myelopathy/tropical spastic paraparesis risk.
- Published
- 2007