Minocycline attenuates T cell and microglia activity to impair cytokine production in T cell-microglia interaction

Minocycline, a tetracycline with anti‐inflammatory properties, has been reported to down‐regulate the activity of microglia, whose activation occurs in inflammatory and degenerative diseases of the central nervous system, such as multiple sclerosis and Alzheimer’s disease. In these disorders, a T cell component is also evident, and we have demonstrated previously that the interaction of activated T cells with microglia led to the substantial increase in tumor necrosis factor α (TNF‐α) levels. Here, we report that minocycline decreases TNF‐α levels produced in human T cell‐microglia interaction. This effect is mediated by a direct action of minocycline on the activated T cells and on microglia, which resulted in the decreased ability of T cells to contact microglia. In correspondence, minocycline decreased the expression on T cells of the CD40 ligand (CD40L), a key molecule regulating the contact‐mediated interaction of T cells with microglia. These results demonstrate that the mechanism of action of minocycline involves not only microglia but also T cells and their subsequent activation of microglia. The capacity of minocycline to down‐regulate CD40L on T cells may provide a new means to target the CD40‐CD40L pathway, which regulates several inflammatory processes.