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

Abstract

Objectives Understanding the determinants of HIV immune control is important for seeking viable HIV prevention, treatment and curative strategies. The antigen‐specific roles of CD8 T cells in controlling primary HIV infection have been well documented, but their abilities to control the latent HIV reservoir is less well studied. Methods The scientific literature on this issue was searched on PubMed. Results Recent reports have demonstrated that CD8 T cells are also involved in the control of viral replication in HIV‐infected individuals receiving antiretroviral therapy (ART). However, based on accumulating evidence, the antiviral role of CD8 T cells in ART patients may not be achieved via an antigen‐specific manner as HIV‐specific CD8 T cells can sense, but not effectively eliminate, cells harbouring intact provirus without first being activated. Our recent study indicated that virtual memory CD8 T cells, a semi‐differentiated component of CD8 T cells, may be involved in the mechanism restraining the HIV DNA reservoir in ART patients. Conclusions In this review, we summarize recent findings on the role of CD8 T cells in controlling HIV, highlighting differences between conventional antigen‐specific and innate‐like CD8 T cells. A better understanding of the roles of CD8 T cells during HIV infection should benefit the informed design of immune‐based treatment strategies.

HIV reservoir: antiviral immune responses and immune interventions for curing HIV infection

“…Although CTLs can inhibit defective proviruses, their ability to control intact proviruses is limited. [ 54 ] The effectiveness of CD8 + T cells in restraining HIV reservoirs remains unclear. In addition, CTL-mediated HIV eradication faces some obstacles, such as HIV immune escape, CD8 + T cell exhaustion, CD8 + T cell compartmentalization and HIV latency.…”

“…The ability of CTLs to effectively recognize and eliminate HIV-infected cells is essential for reducing HIV reservoirs. Although CTLs can inhibit defective proviruses, their ability to control intact proviruses is limited [54] . The effectiveness of CD8 + T cells in restraining HIV reservoirs remains unclear.…”

Mechanism of Viral Suppression among HIV Elite Controllers and Long-Term Nonprogressors in Nigeria and South Africa

“…The primary target of HIV infection is CD4+ T cells, resulting in the massive loss of CD4+ T cells during the early stage of infection, especially in the lymphoid tissue that is associated with the gut [67,95,96]. CD8+ T cells are, however, activated as a host immuno-logical response to elicit cytotoxic effects against HIV infection at this acute stage [97][98][99]. Gray et al [100] investigated the patterns of HIV-1-specific T cells at the acute stage of infection using the gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay to measure the level of responses against the HIV-1 proteome.…”

CCL5-Secreting Virtual Memory CD8+ T Cells Inversely Associate With Viral Reservoir Size in HIV‐1−Infected Individuals on Antiretroviral Therapy

“…Of which, we previously showed that a virtual memory T (T VM ) cells subset, defined by CD44 hi CD122 hi CD49d lo in mice and CD45RA+ killer Ig-like receptors (KIR)+ and/or CD94 natural killer group 2 member A (NKG2A)+ in humans (17,26,27), senses and inhibits the reactivation of HIV-1 reservoir through KIR (28). Thus, T VM cells might represent a bystander CD8+ Tcell subset of interest in terms of constraining the size of HIV-1 reservoirs (29). The clinical relevance and functionality of this subset warrants further investigation.…”