HIV Controllers Exhibit Effective CD8⁺ T Cell Recognition of HIV-1-Infected Non-activated CD4⁺ T Cells

Area of Science:

• Immunology
• Virology
• HIV Research

Background:

• Resting CD4+ T-cells harbor persistent HIV reservoirs despite antiretroviral therapy, hindering HIV cure.
• Identifying mechanisms to eliminate infected cells is crucial for eradicating HIV.

Purpose of the Study:

• To investigate if CD8+ T-cells can recognize and eliminate HIV-infected CD4+ T-cells before the establishment of viral latency.
• To understand the role of early viral particle recognition by CD8+ T-cells in controlling HIV reservoirs.

Main Methods:

• Assessing immune synapse formation, degranulation, cytokine production, and killing of infected CD4+ T-cells by CD8+ T-cells.
• Analyzing HLA-I presentation of peptides derived from incoming viral particles.
• Comparing CD8+ T-cell responses between HIV controllers and progressors.

Main Results:

• CD8+ T-cells recognize and kill non-activated, HIV-infected CD4+ T-cells.
• Recognition occurs independently of de novo protein production, triggered by HLA-I presentation of peptides from incoming viral particles.
• This recognition happens after both cell-free and cell-to-cell HIV infection.
• CD8+ T-cells from HIV controllers show more effective recognition than those from progressors.

Conclusions:

• HIV-infected CD4+ T-cells can be targeted by CD8+ T-cells immediately after HIV entry, prior to reverse transcription and latency.
• This early immune targeting mechanism may contribute to reducing the size of the HIV reservoir.
• The findings suggest a potential strategy for immune-based HIV reservoir reduction.