How memory T cells stay silent when their help is not neededNews
Fiamma Salerno, from the Wolkers lab, unravelled how the cytokine production of memory T cells is actively suppressed when no danger is sensed. The work is published in Nature Immunology. The magazine dedicated an editorial to this paper.
T cells protect us from recurring infections. They circulate through our body in a constant search for cells that are infected with viruses or bacteria, but also for cells that are on the way to become tumor cells. T cells also provide local protection from infections by scanning the organs in which a specific infection occurred before, such as the skin or the lung. While patrolling our body, T cells are silent. However, they maintain in a ready-to-respond state. Whenever memory T cells encounter a cell, they immediately produce toxic molecules such as cytokines, which enables them to clear infected cells early during infection. Memory T cells therefore prevent the spreading of pathogens and help to keep us healthy.
This ready-to-respond rate of memory T cells also comes with a risk: if they produce the cytokines at the wrong time and place, these toxic molecules can do much harm and induce severe tissue damage. Fiamma Salerno from the Wolkers lab now unravelled how the cytokine production of memory T cells is actively suppressed when no danger is sensed, a study that is now published in Nature Immunology.
Memory T cells can immediately respond to infections because they persistently express pre-formed cytokine messenger RNA. This messenger RNA template allows them to instantaneously produce the cytokines. The Wolkers lab now uncovered that the RNA binding protein ZFP36L2 binds to specific sequences in the mRNA in resting memory T cells to block the translation into proteins. This RNA binding protein thus acts as a save guard to prevent aberrant cytokine production to occur.
Upon activation of the memory T cells, ZFP36L2 loses its binding to the messenger RNA and the preformed messenger RNA provides now the possibility for the cells to produce cytokines instantaneously, without losing precious time by first having to initiate the generation of mRNA. The mechanism that Dr. Salerno revealed in her study thus allows for swift recall responses to infection, which is critical to prevent pathogen spreading.
This work is financed by the Netherlands Organisation for Scientific Research (NWO).