CD38: an ecto-enzyme with functional diversity in T cells.

Area of Science:

• Immunology
• Cell Biology
• Virology

Background:

• CD38 is a T lymphocyte activation marker often upregulated in chronic viral infections.
• Its precise role in different T cell subsets and its impact on cellular metabolism and function remain unclear.

Purpose of the Study:

• To investigate CD38 expression and function in naïve and effector T cells from healthy donors and people with HIV (PWH).
• To assess CD38's impact on nicotinamide adenine dinucleotide (NAD)+ levels, mitochondrial function, and cytokine production.
• To evaluate the therapeutic potential of CD38 inhibition.

Main Methods:

• Flow cytometry was used to analyze CD38 expression in T cell subsets from PBMCs.
• Intracellular NAD+ levels, mitochondrial membrane potential, and metabolic activity were measured.
• The effect of CD38 inhibition using the small molecule 78c was examined.

Main Results:

• Naïve T cells exhibited higher CD38 expression, correlating with lower NAD+ levels, reduced mitochondrial function, and decreased metabolic activity.
• CD38 inhibition in naïve T cells enhanced metabolic function and mitochondrial parameters.
• In people with HIV, CD38 expression was elevated on Gag-specific cytokine-producing effector T cells, and CD38 inhibition reduced cytokine production.

Conclusions:

• In naïve T cells, high CD38 expression is linked to reduced metabolic activity.
• In effector T cells, CD38 contributes to immunopathogenesis by promoting inflammatory cytokine production.
• CD38 represents a potential therapeutic target for managing immune activation in chronic viral infections.