HIV-1 replication activates CD4+ T cells with specificities for persistent herpes viruses.
Hyperactivation of CD4+ T cells is a hallmark of untreated HIV-1 infection. The antigenic specificities of activated CD4+ T cells and the underlying mechanisms leading to their activation remain thus far elusive. We report here that during HIV rebound the dynamics of HIV-specific CD4+ T cells is highly correlated with the dynamics of CD4+ T cells specific for persistent antigens derived from various members of the herpes virus family, whereas CD4 responses towards non-persistent antigens were unaffected by HIV replication. Notably, the dynamics of HIV and herpes viral antigen-specific CD4+ T cells responses correlated with the expression level of activation markers on dendritic cells (DCs) and activated DCs were more potent in restimulating memory T cells. These data strongly suggest that HIV replication costimulates activation of CD4+ T cells specific for persistent herpes viral antigens via activation of DCs. We propose that a large proportion of activated T cells during untreated HIV infection may be specific for herpes viral antigens and identify a novel mechanism contributing to chronic immune activation in untreated HIV-1 infection.
Institute of Microbiology, ETH Zurich, Zurich, Switzerland.
Anna
A
Haas
Manuela
M
Rehr
Frederik
F
Graw
Peter
P
Rusert
Walter
W
Bossart
Herbert
H
Kuster
Alexandra
A
Trkola
Huldrych F
HF
Günthard
Annette
A
Oxenius
D000328:Adult; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D006564:Herpesviridae / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged
D000956:Antigens, Viral