CD8+ T cells are activated in an antigen-independent manner in HIV-infected individuals

• Published in: The Journal of immunology (1950) Vol. 192; no. 4; pp. 1732 - 1744
• Main Authors: Bastidas, Sonia, Graw, Frederik, Smith, Miranda Z, Kuster, Herbert, Günthard, Huldrych F, Oxenius, Annette
• Format: Journal Article
• Language: English
• Published: United States 15.02.2014
• Subjects: Adult; Anti-HIV Agents - therapeutic use; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Proliferation; Dendritic Cells - immunology; Female; HIV Infections - drug therapy; HIV Infections - immunology; HIV-1 - immunology; Humans; Interleukin-15 - metabolism; Lipopolysaccharides; Lymphocyte Activation - immunology; Male; Middle Aged
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1302027

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.