Die Rolle von natürlichen Killer T Zellen in entzündlicher Lebererkrankung: Untersuchung des Schutzmechanismus vor Concanavalin-A induzierter Hepatitis
Final Report Abstract
This project aimed to investigate the role of natural killer T (NKT) cells in inflammatory liver disease. When I joined Dr. Kumar's group, work on the original main question, how a major type II NKT cell subset, recognizing sulfatide, mediates protection from murine autoimmune hepatitis, was already ongoing. Hence, I focused on further characterization of this subset and its role in hepatic ischemic reperfusion injury (IRI). Analysis of the TCR Vα and Vß gene usage by sulfatide-reactive type II NKT cells from murine liver revealed an oligoclonal TCR Vα and Vß gene repertoire, distinct from that of type I NKT cells. Strikingly restricted, their TCRα-chain is characterized by predominant usage of Vα3/Vα1 and Jα7/Jα9/Jα12 gene segments with defined CDR3a regions. Also their Vß gene repertoire is limited, utilizing Vß8.1/Vß3.1 and predominantly the Jß2.7 gene segment, with few dominant clonotypes of restricted CDR3ß lengths. Of note, in both TCRα- and ß-chains, a part of the CDR3 regions is encoded by germline. Collectively, these findings emphasize the innate-like nature of type II NKT cells with antigenspecificity for sulfatide. This is the first study of the TCR repertoire of a major self-glycollpid-reactive type II NKT cell subset and has further implications on TCR recognition of ß-linked glycolipids in general. Moreover, it provides a new tool for tracking and controlling this NKT cell subset. Involved in protection from autoimmune diseases and suppression of anti-tumor immunity. Examination of the roles for distinct NKT cell subsets in the murine liver inflammation model of IRI is ongoing. Further investigations on the different NKT cell subsets in human peripheral blood of healthy donors and in patients with inflammatory liver disease are planned.
Publications
- Cross-regulation between distinct Natural Killer T cell subsets influences immune response to self and foreign antigens. J Cell Physiol 2009; 218(2): 246-50
Arrenberg P, Halder R, Kumar V
