It has recently been demonstrated that toll-like receptors (TLRs) can recognize structural conserved motifs carried by circulating microbial products and lead to systemic immune responses in individuals infected with HIV-1. TLRs have been detected in CD8+ T cells at either a protein or RNA level. The role of TLRs on CD8+ T cells involved in the host's immune responses during HIV-1 infection has not been well characterized. In this study, we analyzed expression of TLR4, TLR5, TLR7, and TLR8 in CD8+ T cells in HIV-1 infection. All these four TLRs could be detected in CD8+ T cells, but only TLR7 in CD8+ T cells from HIV-1-infected individuals showed a higher expression level compared with that from healthy individuals (p<0.05). The function of TLR7 in CD8+ T cells was then investigated. We found that TLR7 ligand responsiveness significantly increased the expression of immune activation markers on purified CD8+ T cells in HIV-1-infected individuals compared with healthy controls. And the levels of these markers were equivalent to those achieved by CD8+ T cells from peripheral blood mononuclear cells (PBMCs). However, we also observed that TLR7 ligand stimulated significant IFN-γ production by CD8+ T cells in an accessory cell-dependent manner. Therefore, although CD8+ T cells can be directly activated by TLR7, accessory cells must play an essential role in the activation of effective functions such as IFN-γ production. These findings suggest that the abnormal expression of TLR7 in CD8+ T cells from HIV-1-infected individuals may contribute to the abnormal immune activation in HIV-1 infection and play an important role in HIV-1 pathogenesis.
ASJC Scopus subject areas
- Infectious Diseases