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.
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.
Department of Immunology, Wright-Fleming Institute, Imperial College, Norfolk Place, London, UK.
Alison M
AM
Vine
Adrian G
AG
Heaps
Lambrini
L
Kaftantzi
Angelina
A
Mosley
Becca
B
Asquith
Aviva
A
Witkover
Gillian
G
Thompson
Mineki
M
Saito
Peter K C
PK
Goon
Laura
L
Carr
Francisco
F
Martinez-Murillo
Graham P
GP
Taylor
Charles R M
CR
Bangham
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015490:HTLV-I Infections / Q000276:immunology* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000302:isolation & purification*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load