Virtual memory CD8+ T cells restrain the viral reservoir in HIV-1-infected patients with antiretroviral therapy through derepressing KIR-mediated inhibition

The role of CD8 T cells in controlling HIV beyond the antigen‐specific face

“…We also observed limited killing capability of NK cells towards HIV‐infected cells, while Tvm cells exhibit a much stronger lytic activity compared with that of CTLs. This indicates that Tvm cells are crucial in controlling the HIV reservoir via both their T‐cell and innate‐cell characteristics [21]. Our results may explain why intact provirus and HIV epitopes are not shaped by CTLs and why CD8 T cells are crucial in controlling HIV rebound in patients receiving ART.…”

“…These data indicate that CTLs can effectively target cells containing defective HIV‐1 proviruses and ultimately shape the defective HIV‐1 proviral landscape, while other subset(s) of CD8 T cells may play a role in controlling latent HIV reservoir activation, residual viral replication, and, possibly, reservoir elimination in ART‐treated patients. Our recent study explored the roles of Tvm cells in restraining latent HIV reservoirs [21]. We found that Tvm cells increase in frequency and quantity in ART‐treated patients, which correlates with reduced latent viral reservoirs based on HIV DNA levels, including both defective and intact provirus.…”

“…Meanwhile, Tvm cells express TCR molecules but are poor responders to TCR stimulation, instead exerting their bystander killing in a KIR/NKG2A‐dependent manner [18]. We observed that Tvm cells are insensitive to HIV‐peptide stimulation, with their superior killing capability being mainly dependent on KIR signalling [21]. In other studies, NKG2D‐expressing cells, including CD8 T cells, are also involved in clearance of HIV‐infected target cells in an antigen‐independent manner [50].…”

“…Previous studies have explored the protective effects of Tvm cells against viral and bacterial pathogens [19,20]. We found that Tvm cells, as distinct from CTLs, can restrain the viral reservoir in HIV‐infected patients receiving ART [21]. Tvm cells are an important component of the adaptive immune response during HIV/SIV infection.…”

Aging With T Cells

“…T-cell senescence and T-cell exhaustion (Figure 2). Together, these changes are speculated to impair the T-cell response against infections, as has been shown in aged mice in primary [74][75][76][77][78] and secondary [79] T-cell responses against infection, and studies in humans showed similar results [80][81][82]. Thus, the development and accumulation of immunosenescent T cells during the process of aging is thought to be an important mediator for increased susceptibility to infectious disease in older adults.…”