CD8+ T cells in HIV control, cure and prevention

Abstract

HIV infection can be effectively treated by lifelong administration of combination antiretroviral therapy , but an effective vaccine will likely be required to end the HIV epidemic. Although the majority of current vaccine strategies focus on the induction of neutralizing antibodies, there is substantial evidence that cellular immunity mediated by CD8 + T cells can sustain long-term disease-free and transmission-free HIV control and may be harnessed to induce both therapeutic and preventive antiviral effects. In this Review , we discuss the increasing evidence derived from individuals who spontaneously control infection without antiretroviral therapy as well as preclinical immunization studies that provide a clear rationale for renewed efforts to develop a CD8 + T cell-based HIV vaccine in conjunction with B cell vaccine efforts. Further, we outline the remaining challenges in translating these findings into viable HIV prevention, treatment and cure strategies.

Comprehensive analysis of HIV elite controllers’ and progressors’ transcriptional profiles from CD8+T lymphocytes demonstrates heterogeneity of pathways and master regulators, which may be essential for disease nonprogression

“…Little is known regarding the mechanisms governing viral control in ECs (11, 13, 18–22, 24), but it appears that cytotoxic and noncytotoxic responses of CD8 + lymphocytes play a major role. Naive CD8 + T lymphocytes recognize MHC-I restricted HIV antigens presented by dendritic cells in lymph nodes that cause their activation, proliferation, and differentiation into cytotoxic T lymphocytes.…”

“…Thus, CD8 + lymphocytes can also exhibit noncytotoxic anti-HIV functions through the secretion of chemokines that compete with HIV particles for the corresponding coreceptors (19). CD8 + lymphocytes from ECs have T-cell receptors capable of broader cross-recognition of mutated epitopes from HIV gag antigens, which may be a consequence of the presence of HLA-I polymorphisms, e.g., HLA-B*57 and B*27, that influence the selection of T cell clones in the thymus (18, 19, 22, 32). CD8 + lymphocytes from ECs do not demonstrate an “exhaustion” state and have preserved functions related to cytotoxic and noncytotoxic responses (18, 19, 22, 24), including the ability to degranulate and secrete cytokines with anti-HIV effects, such as MIP-1α/β, RANTES, IFN-γ, TNF-α, and IL-2.…”

“…Chronic infection also causes the dysfunction or “exhaustion” of CD8 + lymphocytes, which is characterized by increased expression of inhibitory immune checkpoints PD-1, Lag-3, and Tim-3 on the surface of cells and decreased ability of CD8 + cells to proliferate, secrete cytokines, and induce cytotoxicity (17). The high mutation rate of HIV, immune exhaustion and the loss of CD4 + and CD8 + cells make further immune responses ineffective with subsequent progression to AIDS (18). However, the time from infection to the development of AIDS can vary significantly among patients.…”

“…The group, called elite controllers (ECs), demonstrates the best control of viral replication with a viral load less than 50 copies/ml while maintaining CD4 cell counts from 200 to 1000/ml. Little is known about the mechanisms of viral control in ECs (11, 13, 18–24), but it seems that host and viral factors, as well as various cell types, may be involved in control, and the cellular response of CD8 + lymphocytes has a major role.…”

The COVID-19 pandemic through eyes of a NYC fertility center: a unique learning experience with often unexpected results

“…Moreover, the widely feared additional wave of COVID-19 and flu-infections in the winter appears less likely, especially if an effective influenza vaccine is offered this year. That cellular immunity can play a significant role in preventing viral diseases has recently also been recognized in conjunction with HIV [ 21 ].…”