The avidity and lytic efficiency of the CTL response to HTLV-1.
In human T-lymphotropic virus type 1 (HTLV-1) infection, a high frequency of HTLV-1-specific CTLs can co-exist stably with a high proviral load and the proviral load is strongly correlated with the risk of HTLV-1-associated inflammatory diseases. These observations led to the hypothesis that HTLV-1 specific CTLs are ineffective in controlling HTLV-1 replication but contribute to the pathogenesis of the inflammatory diseases. But evidence from host and viral immunogenetics and gene expression microarrays suggests that a strong CTL response is associated with a low proviral load and a low risk of HAM/TSP. Here, we quantified the frequency, lytic activity and functional avidity of HTLV-1-specific CD8(+) cells in fresh, unstimulated PBMCs from individuals with natural HTLV-1 infection. The lytic efficiency of the CD8(+) T cell response-the fraction of autologous HTLV-1-expressing cells eliminated per CD8(+) cell per day-was inversely correlated with both the proviral load and the rate of spontaneous proviral expression. The functional avidity of HTLV-1-specific CD8(+) cells was strongly correlated with their lytic efficiency. We conclude that efficient control of HTLV-1 in vivo depends on the CTL lytic efficiency, which depends in turn on CTL avidity of Ag recognition. CTL quality determines the position of virus-host equilibrium in persistent HTLV-1 infection.
Kattan
Tarek
T
Department of Immunology, Wright-Fleming Institute, Imperial College London, United Kingdom.
MacNamara
Aidan
A
Rowan
Aileen G
AG
Nose
Hirohisa
H
Mosley
Angelina J
AJ
Tanaka
Yuetsu
Y
Taylor
Graham P
GP
Asquith
Becca
B
Bangham
Charles R M
CR
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002908:Chronic Disease; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016356:Gene Products, tax / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology / Q000473:pathology / Q000821:virology; D015493:Paraparesis, Tropical Spastic / Q000276:immunology / Q000473:pathology / Q000821:virology; D011533:Proviruses / Q000235:genetics / Q000276:immunology; D051381:Rats; D019562:Viral Load
D018984:Epitopes, T-Lymphocyte; D016356:Gene Products, tax