title: In vivo T lymphocyte dynamics in humans and the impact of human T-lymphotropic virus 1 infection.
abstract: Human T-lymphotropic virus type 1 (HTLV-1) is a persistent CD4+ 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 CD4+CD45RO+ and CD8+CD45RO+ T lymphocyte proliferation was elevated in HTLV-1-infected subjects compared with controls, with an extra 10(12) lymphocytes produced per year in an HTLV-1-infected subject. The in vivo proliferation rate of CD4+CD45RO+ cells also correlated with ex vivo viral expression. Finally, the inflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis was associated with significantly increased CD4+CD45RO+ 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.
authors.affiliation: Department of Immunology, Imperial College, London W2 1PG, United Kingdom. b.asquith@imperial.ac.uk
authors.forename: Becca
authors.initials: B
authors.lastname: Asquith
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Angelina J
authors.initials: AJ
authors.lastname: Mosley
authors.forename: Catherine M
authors.initials: CM
authors.lastname: de Lara
authors.forename: Diana L
authors.initials: DL
authors.lastname: Wallace
authors.forename: Andrew
authors.initials: A
authors.lastname: Worth
authors.forename: Lambrini
authors.initials: L
authors.lastname: Kaftantzi
authors.forename: Kiran
authors.initials: K
authors.lastname: Meekings
authors.forename: George E
authors.initials: GE
authors.lastname: Griffin
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: David F
authors.initials: DF
authors.lastname: Tough
authors.forename: Peter C
authors.initials: PC
authors.lastname: Beverley
authors.forename: Graham P
authors.initials: GP
authors.lastname: Taylor
authors.forename: Derek C
authors.initials: DC
authors.lastname: Macallan
authors.forename: Charles R M
authors.initials: CR
authors.lastname: Bangham
mesh_terms: D002455:Cell Division; D016356:Gene Products, tax / Q000032:analysis; D015490:HTLV-I Infections / Q000276:immunology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D015493:Paraparesis, Tropical Spastic / Q000276:immunology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D016356:Gene Products, tax; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1