The immune control of HTLV-1 infection: selection forces and dynamics.
Cytotoxic T lymphocytes (CTLs) play a central role in the protective immune response to human T-lymphotropic virus 1 (HTLV-1). Here we consider two questions. First, what determines the strength of an individual's HTLV-1-specific CTL response? Second, what controls the rate of expression of HTLV-1 in vivo, which is greater in patients with HAM/TSP than in asymptomatic carriers with the same proviral load? Recent evidence shows that FoxP3+CD4+ T cells are abnormally frequent in HTLV-1 infection, and the frequency of these cells is inversely correlated with the rate of CTL lysis of HTLV-1-infected cells, suggesting that FoxP3+CD4+ cell frequency is an important determinant of the outcome of HTLV-1 infection. There is also new evidence that the rate of expression of HTLV-1 in vivo is associated with the transcriptional activity of the flanking host genome. We suggest that the frequencies of HTLV-1-infected T cell clones in vivo are determined by a dynamic balance between positive and negative selection forces that differ among the clones.
Bangham
Charles R M
CR
Department of Immunology, Imperial College, Norfolk Place, London W2 1PG, UK. c.bangham@imperial.ac.uk
Meekings
Kiran
K
Toulza
Frederic
F
Nejmeddine
Mohamed
M
Majorovits
Endre
E
Asquith
Becca
B
Taylor
Graham P
GP
D016679:Genome, Viral; D005838:Genotype; D015490:HTLV-I Infections / Q000276:immunology* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics; D006801:Humans; D015493:Paraparesis, Tropical Spastic / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019562:Viral Load