Immune cells learn “numbers” from past infections, allowing the body to better deal with future infections of all types

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According to recent work conducted by a joint team of researchers from James Cook University, Charité-Universitätsmedizin Berlin, the Max Planck Institute for Infection Biology, the University of Heidelberg, and the National Institutes of Health, the body’s cells not only learn from the infections they encounter, becoming better able to deal with various infections throughout life, but can also remember numbers.

Dr. Andreas Kupz,
Dr. Andreas Kupz

“For a very long time we have tried to classify memory immune cells on overall function and morphology and have tried to group them based on such features,” James Cook University’s Dr. Andreas Kupz, co-author on the study, told The Speaker. “Although this might make the wealth of information and detail more digestible, it becomes more and more clear, not just from our study, that such ‘average’ is just not good enough anymore. There is a huge heterogeneity even within individual memory immune cell subsets and in the future the focus must be much more directed towards the single cell level.”

T-helper cells, which were the focus of the recent research, help other immune cells by releasing cytokines, messenger substances.

“Our findings demonstrate that every individual T helper cell stably memorizes not only the type but also the amount of a certain cytokine it produces based on the information it receives during an initial infection,” Kupz told us. “Although we did not test the effect of this quantitative cytokine memory on a different infection, it is likely that the amount of cytokine produced will not change because the level of cytokine is predetermined through the amount of a ‘master transcription factor’ within the nucleus of the cell.”

However, T-helper cells don’t learn in the same way we understand people to learn.

“‘Learning’ in this situation is probably best translated with ‘memorizing,’ which in itself is a feature of learning. The learning occurs through maintaining a defined amount of the transcription factor that controls the production of certain cytokines. The cell-specific fine adjustments of this process is still not entirely understood but may involve the control of cytokine receptor expression and/or the activity of downstream signal transduction molecules.”

“Furthermore, we found epigenetic modifications at both the locus of the cytokine and the controlling transcription factor. Hence, we hypothesize that a combination of multiple permissive and repressive epigenetic modifications at several regulatory sites imprints the stable cytokine memory.”

Although dealing with infections does strengthen the body’s ability to deal with later infections — which might be information that could factor into arguments in the current vaccination debate — Kupz was clear that his comments were not to be on the debate, and that vaccination is something he believes is very important and necessary.

“The immunological memory that is generated through exposure to vaccines does in fact often rely on similar ‘learning’ mechanisms. ”

“In my opinion the most important take home message from this study is not so much the applicability of our findings for health and disease but more the gain in overall knowledge about T cell biology,” Kupz speculated on how his work could contribute to the growing body of information about the role of T cells, and how it could potentially lead to strengthening specific immune reactions and to reducing the misdirected immune responses that cause inflammation.

The report, “Individual T helper cells have a quantitative cytokine memory,” was completed by 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, and Max Löhning, and was published in the journal Immunity.