BCL-2 antagonism sensitizes cytotoxic T cell–resistant HIV reservoirs to elimination ex vivo

Abstract

were used immediately if possible or cryopreserved in liquid nitrogen; cells were not left in culture before the initiation of experiments.

Single-cell TCR sequencing reveals phenotypically diverse clonally expanded cells harboring inducible HIV proviruses during ART

“…6d). In addition, our results indicate that HIV-infected cells have the ability to proliferate and differentiate without being eliminated, suggesting that this process can occur in the absence of HIV production as previously reported 38,39 or that these cells can escape immune-mediated killing, as recently suggested by Ren et al 40 .…”

Concanamycin A counteracts HIV-1 Nef to enhance immune clearance of infected primary cells by cytotoxic T lymphocytes

“…The identification of LRAs that induce sufficient HIV gene expression for CTL recognition while maintaining CD4 + T cells in a resting state is a critical need. It is important to note that resting CD4 + T cells may harbor additional mechanisms to resist CTL killing that will need to be addressed (10,70). Our data indicating that CMA is effective at enhancing CTL-mediated clearance is thus far limited to actively infected primary T cells and may not translate to clearance of reactivated resting cells in vivo.…”

“…Thus, the parallel development of improved latency-reversal agents (LRAs) will be needed to achieve a cure. LRAs that achieve sufficient reactivation from latency to sensitize infected cells to CTLs also cause T cell activation ( 10 , 69 , 70 ). The identification of LRAs that induce sufficient HIV gene expression for CTL recognition while maintaining CD4 + T cells in a resting state is a critical need.…”

Editorial: HIV and Cancer Immunotherapy: Similar Challenges and Converging Approaches

“…This incomplete elimination permits subsequent equilibrium phase sculpting of reservoir-harboring cells by immune pressures, which in cancer models has been termed "immunoediting" (25). Analogous to "antigen loss" in tumors models, Huang et al explore the novel concept that during ART cells harboring replication-competent virus undergo clonal expansion with subsequent immunoediting; thereby decreasing CTL susceptibility by selecting for BCL-2 expression (26) and integration sites favoring cell division (27,28). As HIV infection impacts on cellular metabolism and oxidative stress (29,30), immunoediting may also select for an altered cellular lipid antigen composition that, as summarized by Tiwary et al, in oncology models impinges on chronic inflammation by modulating the macrophage M1 to M2 balance (31) and impairs antigen processing in dendritic cells (32); specifically, CD1d antigen loading for natural killer T-cells (NKT) (33).…”