Increased expression of TLR7 in CD8(+) T cells leads to TLR7-mediated activation and accessory cell-dependent IFN-gamma production in HIV type 1 infection.
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-gamma 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-gamma 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.
Song
Yang
Y
Department of Infectious Diseases, Tangdu Hospital Affiliated to the Fourth Military Medical University, Xi'an 710038, PR China.
Zhuang
Yan
Y
Zhai
Song
S
Huang
Dedong
D
Zhang
Ying
Y
Kang
Wenzhen
W
Li
Xinhong
X
Liu
Qingquan
Q
Yu
Qigui
Q
Sun
Yongtao
Y
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D051199:Toll-Like Receptor 7 / Q000276:immunology*; D019562:Viral Load; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007371:Interferon-gamma; D007376:Interleukin-2; D037181:Lectins, C-Type; D008024:Ligands; D051199:Toll-Like Receptor 7; D000099192:CD69 Antigens; C508594:IL2 protein, human; C495348:TLR7 protein, human