Normal T-cell activation in elite controllers with preserved CD4+ T-cell counts.

Area of Science:

• Immunology
• Virology
• Clinical Medicine

Background:

• HIV elite controllers naturally suppress viral load without antiretroviral therapy (ART).
• Previous research indicated persistent immune activation in elite controllers, suggesting ART might be beneficial.
• Elite controllers are not a uniform group; CD4% is a strong predictor of AIDS-related events.

Purpose of the Study:

• To investigate if CD4% can stratify elite controllers (ECs) for ART necessity.
• To analyze T-cell and monocyte phenotypes in ECs based on CD4% levels.

Main Methods:

• Sixteen elite controllers were grouped by CD4% (>40% vs. ≤40%).
• T-cell subsets were analyzed for memory, activation, senescence, costimulation, and exhaustion markers.
• Monocyte subsets and soluble CD14 (sCD14) levels were quantified.

Main Results:

• ECs with preserved CD4% (>40%) exhibited reduced T-cell activation, exhaustion, and senescence markers compared to ECs with lower CD4%.
• These ECs showed normal T-cell phenotypes, similar to seronegative controls.
• ECs with preserved CD4% had lower monocyte activation and a reduced frequency of inflammatory monocytes, maintaining stable CD4% over 6 years.

Conclusions:

• Elite controllers with preserved CD4 T cells display normal immune cell phenotypes, suggesting limited benefit from ART.
• CD4% is a crucial marker for stratifying elite controllers in future studies evaluating ART initiation.