The role of CTLs in persistent viral infection:: Cytolytic gene expression in CD8+ lymphocytes distinguishes between individuals with a high or low proviral load of human T cell lymphotropic virus type 1

被引:68
作者
Vine, AM
Heaps, AG
Kaftantzi, L
Mosley, A
Asquith, B
Witkover, A
Thompson, G
Saito, M
Goon, PKC
Carr, L
Martinez-Murillo, F
Taylor, GP
Bangham, CRM
机构
[1] Univ London Imperial Coll Sci Technol & Med, Wright Fleming Inst, Dept Immunol, London W2 1PG, England
[2] Univ London Imperial Coll Sci Technol & Med, Wright Fleming Inst, Dept Infect Dis, London W2 1PG, England
[3] Johns Hopkins Univ, Johns Hopkins Med Inst, Microarray Core, Baltimore, MD 21205 USA
关键词
D O I
10.4049/jimmunol.173.8.5121
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The proviral load in human T cell lymphotropic virus type 1 (HTLV-1) infection is typically constant in each infected host, but varies by > 1000-fold between hosts and is strongly correlated with the risk of HTLV-1-associated inflammatory disease. However, the factors that determine an individual's HTLV-1 proviral load remain uncertain. Experimental evidence from studies of host genetics, viral genetics, and lymphocyte function and theoretical considerations suggest that a major determinant of the equilibrium proviral load is the CD8(+) T cell response to HTLV-1. In this study, we tested the hypothesis that the gene expression profile in circulating CD8(+) and CD4(+) lymphocytes distinguishes between individuals with a low proviral load of HTLV-1 and those with a high proviral load. We show that circulating CD8(+) lymphocytes from individuals with a low HTLV-1 proviral load overexpressed a core group of nine genes with strong functional coherence: eight of the nine genes encode granzymes or other proteins involved in cell-mediated lysis or Ag recognition. We conclude that successful suppression of the HTLV-1 proviral load is associated with strong cytotoxic CD8(+) lymphocyte activity in the peripheral blood.
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收藏
页码:5121 / 5129
页数:9
相关论文
共 63 条
[1]   Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load [J].
Addo, MM ;
Yu, XG ;
Rathod, A ;
Cohen, D ;
Eldridge, RL ;
Strick, D ;
Johnston, MN ;
Corcoran, C ;
Wurcel, AG ;
Fitzpatrick, CA ;
Feeney, ME ;
Rodriguez, WR ;
Basgoz, N ;
Draenert, R ;
Stone, DR ;
Brander, C ;
Goulder, PJR ;
Rosenberg, ES ;
Altfeld, M ;
Walker, BD .
JOURNAL OF VIROLOGY, 2003, 77 (03) :2081-2092
[2]   The cytotoxic T-lymphocyte response to HTLV-I: The main determinant of disease? [J].
Bangham, CRM ;
Kermode, AG ;
Hall, SE ;
Daenke, S .
SEMINARS IN VIROLOGY, 1996, 7 (01) :41-48
[3]   The immune control and cell-to-cell spread of human T-lymphotropic virus type 1 [J].
Bangham, CRM .
JOURNAL OF GENERAL VIROLOGY, 2003, 84 :3177-3189
[4]   Analysis of total human immunodeficiency virus (HIV)-specific CD4+ and CD8+ T-cell responses:: Relationship to viral load in untreated HIV infection [J].
Betts, MR ;
Ambrozak, DR ;
Douek, DC ;
Bonhoeffer, S ;
Brenchley, JM ;
Casazza, JP ;
Koup, RA ;
Picker, LJ .
JOURNAL OF VIROLOGY, 2001, 75 (24) :11983-11991
[5]   A comparison of normalization methods for high density oligonucleotide array data based on variance and bias [J].
Bolstad, BM ;
Irizarry, RA ;
Åstrand, M ;
Speed, TP .
BIOINFORMATICS, 2003, 19 (02) :185-193
[6]   Inhibition of proliferation by 1-8U in interferon-α-responsive and non-responsive cell lines [J].
Brem, R ;
Oroszlan-Szovik, K ;
Foser, S ;
Bohrmann, B ;
Certa, U .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2003, 60 (06) :1235-1248
[7]   Human CD8+ T cells store RANTES in a unique secretory compartment and release it rapidly after TcR stimulation [J].
Catalfamo, M ;
Karpova, T ;
McNally, J ;
Costes, SV ;
Lockett, SJ ;
Bos, E ;
Peters, PJ ;
Henkart, PA .
IMMUNITY, 2004, 20 (02) :219-230
[8]  
Cavrois M, 1996, ONCOGENE, V12, P2419
[9]   The chemokine receptor CX3CR1 controls homing and anti-viral potencies of CD8 effector-memory T lymphocytes in HIV-infected patients [J].
Combadière, B ;
Faure, S ;
Autran, B ;
Debré, P ;
Combadière, C .
AIDS, 2003, 17 (09) :1279-1290
[10]  
Cosman D, 2001, IMMUNITY, V14, P123, DOI 10.1016/S1074-7613(01)00095-4