Consequently, our findings suggest that CD4+ and CD8+ T cell activation, along with increased Th-1 polarization and IL-16 production, are key phenomena that drive increased T effector, T helper, and T cytotoxic functions, as well as enhanced M1, Th-17, IRS, and neurotoxic immune profiles in the acute phase of severe MDD. This evidence concerns the gene CD8A and major depressive disorder.