Fig. 2.

Enzymatic activity of CD38 molecules leads to internal alterations in CD4⁺ T cells. CD38 catalyzes the conversion of NAD to ADPR, cADPR, and NAADP, which reduces cytoplasmic NAD in CD4⁺ T cells, leading to a chronic Warburg effect that decreases mitochondrial function. The catalytic products of CD38 can activate calcium channels and increase cytoplasmic Ca²⁺ concentrations, further reducing mitochondrial integrity. Depletion of cytoplasmic NAD promotes the Warburg effect and continues to affect mitochondrial function and integrity. Elevated cytoplasmic Ca²⁺ concentrations further increase mitochondrial stress, which ultimately leads to decreased CD4⁺ T cell survival