CD8(+) T-cell responses in HIV controllers: potential implications for novel HIV remission strategies

Immunological studies of spontaneous HIV and simian virus (SIV) controllers have identified virus-specific CD8(+) T cells as a key immune mechanism of viral control. The purpose of this review is to consider how knowledge about the mechanisms that are associated with CD8(+) T cell control of HIV/SIV in natural infection can be harnessed in HIV remission strategies. RECENT FINDINGS: We discuss characteristics of CD8(+) T-cell responses that may be critical for suppressing HIV replication in spontaneous controllers comprising HIV antigen recognition including specific human leukocyte antigen types, broadly cross-reactive T cell receptors and epitope targeting, enhanced expansion and antiviral functions, and localization of virus-specific T cells near sites of reservoir persistence. We also discuss the need to better understand the timing of CD8(+) T-cell responses associated with viral control of HIV/SIV during acute infection and after treatment interruption as well as the mechanisms by which HIV/SIV-specific CD8(+) T cells coordinate with other immune responses to achieve control. SUMMARY: We propose implications as to how this knowledge from natural infection can be applied in the design and evaluation of CD8(+) T-cell-based remission strategies and offer questions to consider as these strategies target distinct CD8(+) T-cell-dependent mechanisms of viral control.