Table 1 Characteristics of CD8⁺ T cell immunity in chronic HIV, HCV, and HBV infection

HIV

Main mechanisms of CD8⁺ T cell adaptation include:

1. T cell exhaustion with:

- Expression of inhibitory receptors, such as LAG-3, TIM-3, TIGIT, 2B4, and CD160

- Impaired effector function

- Reduced frequencies of virus-specific CD8⁺ T cells

- Altered metabolism

- Distinct transcriptional and epigenetic programs

2 Viral escape leading to an impaired antigen recognition

Early initiation of HIV therapy can preserve a certain degree of multifunctionality of HIV-specific CD8⁺ T cells

Regulatory T cells promote T cell exhaustion through IL-10–mediated suppression of T cell proliferation

77, 78, 81

HCV

Heterogeneous T_EX subsets, such as the memory-like TCF-1 + CD127 + PD-1+ and terminally differentiated Eomes^highTOX^highCD127-PD-1+ subsets

TCF-1+ memory-like T cells mount recall responses after successful DAA therapy, but remain functionally restrained compared with classical memory CD8⁺ T cells

Differences between memory-like and bona fide memory CD8⁺ T cells are caused by epigenetic imprinting and transcriptional scarring

Reduced efficacy despite measurable T cell responses in HCV vaccine trials, likely due to viral escape

29, 48, 55–57, 63, 86–89

HBV

Inhibitory molecules are variably expressed, but no correlation with functional impairment

HBV-specific CD8⁺ T cell responses differ depending on antigen specificity

Liver rheostat, lack of costimulation, and TGF-β-associated T cell attenuation are additional mechanisms of the adapted HBV-specific CD8⁺ T cell response

93–96, 105