Charité researchers discover that immune cells can 'remember' numbers
Immunologists from the Charité – Universitätsmedizin Berlin and the Deutsches Rheuma-Forschungszentrum have demonstrated how a single immune cell can 'remember' the quantity of a specific messenger substance it needs to produce. These messenger substances regulate immune responses and inflammatory processes. In the future it may be possible to strengthen a specific immune reaction, while simultaneously reducing misdirected immune responses. The results of their study have been published in the current edition of the journal Immunity*.
The group of Prof. Max Löhning, Deputy Director of the Research Center for ImmunoScience of the Charité, has been conducting research on the maturation and differentiation of T-helper cells. These cells secrete messenger substances, so-called cytokines, that serve to regulate immune responses. The research group has now succeeded in demonstrating that a T-helper cell at the time of its initial activation by way of infection for example not only 'learns' which cytokine it needs to produce, but also in which quantity. T-helper cells stably retain this "quantitative cytokine memory". If the infection is conquered, some of the T-helper cells are then transformed into long-lived memory T cells. Whenever a new infection emerges these memory T cells are activated and again release the same predetermined quantity of cytokine. It was already known that, in principle, T cells can produce different quantities of a messenger substance, but it was assumed that these were randomly distributed and could not be stably 'remembered' in the individual cells.
The researchers also identified a key factor with respect to the retention of "quantitative cytokine memory" of individual T cells. This concerns a transcription factor that exists in a specific quantity in the nucleus of each cell and manifests as a "swimming manufacturing specification". If the transcription factor is present in large quantities, a large quantity of cytokine will also be produced, and vice-versa. The cells stably retain their respective levels of the transcription factor and thus also their cell-specific production amounts of the cytokine.
In the context of an immune response, T-helper cells producing small quantities of a certain cytokine are present, as well as those producing larger quantities. "We assume that in this way a fine adjustment of the immune reaction is achieved, because while the messenger substances are useful, they can cause physical damage in higher doses. At worst, the body's own structures are often attacked or otherwise harmless substances are antagonized", is how Professor Löhning explains the study's findings. "Such occurrences are caused by an overreaction of the immune system. The recently discovered level of quantitative regulation may make it possible to foster only weakly reacting immune cells, and in turn, to attenuate the overall immune response. Conversely, when combating cancer cells and many infections, we would increase the number of highly active immune cells in a targeted manner", he added.
*Caroline Helmstetter, Michael Flossdorf, Michael Peine, Andreas Kupz, Jinfang Zhu, Ahmed N. Hegazy, Maria A. Duque-Correa, Qin Zhang, Yevhen Vainshtein, Andreas Radbruch, Stefan H. Kaufmann, William E. Paul, Thomas Höfer und Max Löhning. Individual T helper cells have a quantitative cytokine memory. Immunity, Januar 2015. doi:10.1016/j.immuni.2014.12.018.
Prof. Dr. Max Löhning
Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie
Charité – Universitätsmedizin Berlin
t. +49 30 2846 0760
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