Cytolytic T Cells in the Immune Response to Mycobacterium tuberculosis

Abstract

Cytolytic T cells (CTL) are of paramount importance in immune defense against tumors and viruses. Work over the past decade has revealed that lysis of infected cells is also involved in protective immunity to bacteria and parasites, including Mycobacterium tuberculosis. Experiments involving gene-deleted mice and the characterization of CTL lines derived from tuberculosis patients suggest an important role of CTL in immunity to tuberculosis. More recently, the identification of an effector pathway of human CTL provided evidence for direct antimicobial activity of CTL. This pathway involves the combined action of the pore-forming perforin and the antibacterial granulysin, both expressed in the granules of CTL. Granulysin binds to the bacterial cell surface, thereby disrupting the membrane and causing osmotic lysis. The relevance of this pathway for protection against intracellular pathogens is suggested by the expression of high amounts of granulysin in tissue from patients with tuberculoid leprosy, which are able to contain the spread of the bacilli. These findings support the current concept of designing novel vaccination strategies which elicit not only CD4+ T helper cells, but also CD8+ CTL with direct antibacterial activity.