In vivo T lymphocyte dynamics in humans and the impact of human T-lymphotropic virus 1 infection.
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.
Asquith
Becca
B
Department of Immunology, Imperial College, London W2 1PG, United Kingdom. b.asquith@imperial.ac.uk
Zhang
Yan
Y
Mosley
Angelina J
AJ
de Lara
Catherine M
CM
Wallace
Diana L
DL
Worth
Andrew
A
Kaftantzi
Lambrini
L
Meekings
Kiran
K
Griffin
George E
GE
Tanaka
Yuetsu
Y
Tough
David F
DF
Beverley
Peter C
PC
Taylor
Graham P
GP
Macallan
Derek C
DC
Bangham
Charles R M
CR
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
D016356:Gene Products, tax; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1