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Published on: May 30, 2013
Elevated Expression of CD160 and 2B4 Defines a Cytolytic HIV-Specific CD8+ T-Cell Population in Elite Controllers
Carolina Pombo1, E John Wherry2, Emma Gostick3
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Insights
Elite HIV controllers maintain functional CD8(+) T cells despite exhaustion markers. A distinct CD8(+) T cell population (CD160(+)2B4(+)) correlates with cytolytic activity, crucial for HIV control.
Area of Science:
- Immunology
- Virology
- Cellular Biology
Background:
- Chronic human immunodeficiency virus (HIV) infection leads to functional exhaustion of virus-specific CD8(+) T cells.
- Elite controllers maintain CD8(+) T cell polyfunctionality and cytolytic capacity, but the extent of their T cell exhaustion is unclear.
Purpose of the Study:
- To assess T cell exhaustion markers (PD-1, Lag-3, CD160, 2B4) in HIV elite controllers and chronic progressors.
- To identify distinct CD8(+) T cell populations associated with HIV control.
Main Methods:
- Flow cytometry was used to analyze coexpression of exhaustion markers (PD-1, Lag-3, CD160, 2B4) on HIV-specific CD8(+) T cells.
- Perforin expression was measured to assess cytolytic capacity.
Main Results:
- Elite controllers and chronic progressors showed comparable proportions of potentially exhausted HIV-specific CD8(+) T cells (PD1(+)CD160(+)2B4(+)).
- Elite controllers possess a unique population of HIV-specific CD160(+)2B4(+) CD8(+) T cells associated with higher cytolytic capacity (perforin expression).
- This CD160(+)2B4(+) population is less common in chronic progressors.
Conclusions:
- Coexpression of CD160 and 2B4 identifies a critical population of cytolytic CD8(+) T cells.
- This distinct CD8(+) T cell subset plays a significant role in the elite control of HIV infection.
Abstract:
During chronic human immunodeficiency virus (HIV) infection, virus-specific CD8(+) T cells become functionally exhausted. Unlike most chronically infected individuals, elite controllers of HIV retain CD8(+) T-cell polyfunctionality and cytolytic capacity. It remains unclear whether elite controllers manifest T-cell exhaustion similar to subjects with chronic progression of HIV infection. Here we assessed coexpression of PD-1, Lag-3, CD160, and 2B4 as a measure of T-cell exhaustion in a cohort of elite controllers and in chronic progressors. We found that elite controllers have a high proportion of potentially exhausted (PD1(+)CD160(+)2B4(+)) HIV-specific CD8(+) T cells that is comparable to the proportion in chronic progressors. However, elite controllers also harbor a population of HIV-specific CD160(+)2B4(+) CD8(+) T cells that correlates with cytolytic capacity, as measured by perforin expression, a population not commonly present in chronic progressors. We therefore propose that coexpression of CD160 and 2B4 delineates a population of cytolytic CD8(+) T cells important for the control of HIV.
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