DeutschClonal immune memory in the innate immune system
The fight against acute infections is achieved in part by the dramatic expansion of previously rare antigen-specific cells of the adaptive immune system. Through this so-called clonal expansion, many identical antigen-specific cells are generated within a very short time that attack the pathogen and resolve the infection. Some of these cells can survive for many years, forming a long-lasting immune memory. In a paper recently published in Nature Immunology, scientists led by Chiara Romagnani and Timo Rückert describe their surprising discovery that natural killer (NK) cells of the innate immune system also form a long-lived immune memory against the human cytomegalovirus (HCMV) by clonal expansion.
The group had shown in a previous paper that NK cells also specifically recognise viral antigens from HCMV. These bind to the receptor CD94/NKG2C, thereby activating the NK cells and inducing their development towards adaptive NK cells. Based on these results, researchers were now able to demonstrate that this specific activation, in combination with pro-inflammatory cytokines, permanently influences the inflammatory memory of NK cells. These NK cells are epigenetically shaped, i.e. the accessibility of their DNA changes in such a way that certain genes are permanently switched on or off, which influences the properties and functions of these cells. It was particularly surprising that the adaptive NK cells imprinted in this way in HCMV-infected people are maintained for years as clonal expansions.
These findings raise many new questions about selection factors and the role of epigenetic features in the clonal competition of immune cells, i.e. why individual NK cells proliferate more than others. These and other questions are being investigated as part of an ERC Advanced Grant recently awarded to Chiara Romagnani. In addition to its importance for viral infections, the inflammatory memory of NK cells could also be relevant for chronic inflammatory diseases, which the group is investigating in the context of juvenile idiopathic arthritis.
