How do lymphocytes eliminate unwanted cells? This review explores the mechanisms of lymphocyte-mediated cytotoxicity, focusing on the granule exocytosis and Fas pathways. The granule exocytosis pathway uses perforin to deliver granzymes to target cells, initiating DNA fragmentation and apoptosis. Fas/FasL system activates cell death, also playing a role in lymphocyte-mediated killing. Granzymes A and B induce cell death through distinct, nonoverlapping pathways, providing multiple avenues for cytotoxic action. The interplay between granule exocytosis and Fas/FasL is essential for immune regulation. These two cytotoxic systems work in concert. Understanding these cytotoxic systems opens avenues for therapeutic interventions in autoimmune diseases and graft-versus-host disease. However, suppressing these pathways may increase viral susceptibility or decrease tumor cell killing. The review provides essential context for understanding immune function and developing targeted therapies.
This review on lymphocyte-mediated cytotoxicity is ideally suited for Annual Review of Immunology, enhancing the journal's comprehensive coverage of immune mechanisms and their therapeutic implications. By summarizing current understanding of cytotoxic pathways, the article serves the journal’s goal of providing insights into immunology.