CD8+ T cells are activated in an antigen-independent manner in HIV-infected individuals.
Hyperactivation of T cells, particularly of CD8(+) T cells, is a hallmark of chronic HIV 1 (HIV-1) infection. Little is known about the antigenic specificities and the mechanisms by which HIV-1 causes activation of CD8(+) T cells during chronic infection. We report that CD8(+) T cells were activated during in vivo HIV-1 replication irrespective of their Ag specificity. Cytokines present during untreated HIV-1 infection, most prominently IL-15, triggered proliferation and expression of activation markers in CD8(+) T cells, but not CD4(+) T cells, in the absence of TCR stimulation. Moreover, LPS or HIV-1-activated dendritic cells (DCs) stimulated CD8(+) T cells in an IL-15-dependent but Ag-independent manner, and IL-15 expression was highly increased in DCs isolated from viremic HIV-1 patients, suggesting that CD8(+) T cells are activated by inflammatory cytokines in untreated HIV-1 patients independent of Ag specificity. This finding contrasts with CD4(+) T cells whose in vivo activation seems biased toward specificities for persistent Ags. These observations explain the higher abundance of activated CD8(+) T cells compared with CD4(+) T cells in untreated HIV-1 infection.
Institute of Microbiology, ETH Zurich, 8093 Zurich, Switzerland;
Sonia
S
Bastidas
Frederik
F
Graw
Miranda Z
MZ
Smith
Herbert
H
Kuster
Huldrych F
HF
Günthard
Annette
A
Oxenius
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism*; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged
D019380:Anti-HIV Agents; D019409:Interleukin-15; D008070:Lipopolysaccharides