CD8+ T-Cell-Derived Tumor Necrosis Factor Can Induce Tissue Factor Expression on Monocytes.

Area of Science:

• Immunology
• Virology
• Cardiovascular Science

Background:

• CD8+ T cells and monocytes are activated during human immunodeficiency virus (HIV) infection.
• These immune cells colocalize in the aortas of simian immunodeficiency virus-infected nonhuman primates, suggesting a role in cardiovascular complications.

Purpose of the Study:

• To investigate the hypothesis that CD8+ T cells promote atherosclerosis through paracrine actions on monocytes.
• To elucidate the specific mechanisms by which CD8+ T cells influence monocyte behavior in the context of HIV infection.

Main Methods:

• Stimulation of CD8+ T cells via the T-cell receptor.
• Assessment of monocyte activation and tissue factor expression.
• Evaluation of the role of tumor necrosis factor in mediating the observed effects.

Main Results:

• T-cell receptor-stimulated CD8+ T cells induce monocytes to express tissue factor.
• Tissue factor expression by monocytes is a key procoagulant and proatherosclerotic event.
• Tumor necrosis factor was identified as both necessary and sufficient for mediating this CD8+ T cell-induced monocyte activation.

Conclusions:

• CD8+ T cells can exert a proatherosclerotic effect on monocytes during HIV infection.
• The interaction involves the induction of tissue factor expression in monocytes, driven by tumor necrosis factor.
• These findings suggest that targeting the CD8+ T cell-monocyte interaction and tumor necrosis factor signaling may offer therapeutic strategies for HIV-associated atherosclerosis.