Part of the innate immune system is natural killer cells. The role of these cells is to detect virus-infected cells and destroy them. With detection of an infection, a small subset of the most effective killer cells is identified and selectively expanded, as a team from the Technical University of Munich (TUM) has now been able to show for the first time. This discovery could represent a simple and evolutionary ancient form of immunological memory.
Cytomegalovirus (CMV) infects more than half of the global population, which remains in the body for life. Usually, these infections do not produce any symptoms. Together with T cells, natural killer cells (NKs) effectively keep the virus in check, although it can cause severe illnesses in individuals with a weakened immune system. NKs possess surface molecules that identify CMV-infected cells, including the receptor Ly49H in mice. It is known that NKs equipped with this receptor (Ly49H-NKs) are especially effective at destroying CMV-infected cells.
The research team leader at TUM's Institute of Medical Microbiology Immunology and Hygiene, Dr. Veit Buchholz and his colleague Dr. Simon Grassmann set out to determine what exactly happens to these Ly49H-NKs during a CMV infection. To achieve this, the two researchers tracked immune responses derived from individual Ly49H-NKs in CMV-infected mice.
The researchers discovered that replication of individual Ly49H-NKs was remarkably varied - this variation correlated with distinct surface expression levels of Ly49H itself. Cells with higher Ly49H expression expanded more and were thus able to combat CMV more effectively. This trait seemed to be heritable, with the descendants of an NK resembling their "parent" cells in terms of Ly49H receptor levels. Previously, scientists have observed the inheritance of quantitative traits in NKs.
Grassmann reported that the exciting aspect was that, even after the peak of the immune response, killer cells expressing high amounts of Ly49H remained detectable at higher numbers. Explaining further, he said that this is an essential indication of the existence of a simple immunological memory based on NKs.
When there is a selection mechanism available that multiplies and then preserves the most active cells for fighting an infection, immunological memory can only work. According to Buchholz, they revealed that in NKs, which are part of the evolutionary ancient, innate immune system, the quantity of receptor alone is a sufficient criterion to drive selection at a single level. This finding could be significant for humans since human NKs possess an equivalent receptor which plays an essential role during CMV infection.
Grassmann developed the appropriate tool to track individual NKs in living organisms, together with medical student Ludwig Pachmayr, within the context of TUM's "Translational Medicine" doctoral program. The researchers are keen to find out how NKs transmit the information about receptor quantity to their descendants. NKs are considered a possible alternative to T cells for immunotherapy of infections and tumor diseases.
