Comparative Analysis of the Capacity of Elite Suppressor CD4 ⁺ and CD8 ⁺ T Cells To Inhibit HIV-1 Replication in Monocyte-Derived Macrophages

Abstract

Elite controllers or suppressors (ESs؉ T cell response effective against infected macrophages is an outcome to consider in rational vaccine design.

Nef Is Dispensable for Resistance of Simian Immunodeficiency Virus-Infected Macrophages to CD8 + T Cell Killing

“…A recent report demonstrated that freshly sorted, SIV-specific CD8 ϩ T cells had the ability to suppress viral replication and eliminate SIV-infected CD4 ϩ T cells after 2 days of infection but were not able to eliminate the majority of SIV-infected macrophages (13). Another study demonstrated that viral replication in HIV-1-infected macrophages could be considerably suppressed 5 to 7 days after infection by ex vivo freshly sorted bulk CD8 ϩ T cells (14). These studies conflict with previous reports that have shown that CD8 ϩ T cell lines or clones can significantly suppress viral replication in HIV/ SIV-infected macrophages in a short time frame (15,16).…”

“…Interestingly, autologous bulk CD8 ϩ T cells and CD4 ϩ T cells from human elite controllers suppressed viral replication in HIV-1-infected macrophages within 5 to 7 days (14). However, within this window of time macrophages were able to spread infection to CD4 ϩ T cell effectors (14). Therefore, slow killing of macrophages is likely to be of little consequence in cellmediated control of viral replication in infected individuals.…”

“…Previously, it has been shown that primary CD8 ϩ T cell clones and CD8 ϩ T cell lines suppress HIV-1 and SIV replication in macrophages (14)(15)(16). Interestingly, autologous bulk CD8 ϩ T cells and CD4 ϩ T cells from human elite controllers suppressed viral replication in HIV-1-infected macrophages within 5 to 7 days (14). However, within this window of time macrophages were able to spread infection to CD4 ϩ T cell effectors (14).…”

“…Therefore, understanding whether these cells succumb to CD8 ϩ T cell killing is important in the design of strategies to cure HIV-1 infection (1-3, 9, 28). Previously, it has been shown that primary CD8 ϩ T cell clones and CD8 ϩ T cell lines suppress HIV-1 and SIV replication in macrophages (14)(15)(16). Interestingly, autologous bulk CD8 ϩ T cells and CD4 ϩ T cells from human elite controllers suppressed viral replication in HIV-1-infected macrophages within 5 to 7 days (14).…”

“…No significant differences were detected in the ability of different SIV-specific CD8 ϩ T cells to eliminate or suppress viral replication in WT-infected target cells. As a positive control, SIV-specific CD8 ϩ T cell lines were generated and used to coculture macrophages infected at a high MOI, resulting in a complete elimination of the target cells, as other investigators have previously shown (data not shown) (14,15).…”