Immune Cells In A Tug Of War For Survival

To survive and maintain immune memory, T-cells need to compete with innate lymphoid cells for a key protein called IL-7.

AsianScientist (Aug. 1, 2017) – In a study published in Immunity, researchers have found that T-cells compete with a rare and recently discovered type of immune cell for a protein needed for survival.

The study of the immune system has produced many life-saving discoveries, the greatest of which is arguably the concept of immunization and immunological memory. Vaccines protect us by stimulating specific immune cell populations—B and T-cells.

The ingredients of vaccines are relatively short-lived, but the protective effects of the vaccine can last for many decades because immune cells are maintained through a process called homeostasis. The homeostatic survival of B- and T-cells is not only important after vaccination, but also in old age when production of B- and T-cells slows.

To survive, these immune cells need to bind to a protein called interleukin-7 (IL-7) via the IL-7 receptor (IL-7R) lying on their surface. However, it is unclear how the body regulates the amount of available IL-7. The question was compounded by the difficulty of measuring IL-7 levels in living organisms—traditional methods of immunohistochemistry or immunofluorescence were inadequate to even detect, let alone quantify, IL-7 in the tissue of mice used for laboratory research.

In this study, the team led by Professor Charles D. Surh, director of the Academy of Immunology and Microbiology (AIM) at the Institute for Basic Science (IBS), used mice lacking the IL-7R so that IL-7 could accumulate to abnormally high levels in the mice. These high levels were sufficient to drive T-cell homeostatic proliferation.

Subsequently, the group replaced various IL-7R-expressing cell types and monitored IL-7 levels until homeostasis was restored. Their results clearly indicated that in addition to T-cells, a rare and recently discovered immune cell known as the innate lymphoid cells (ILCs) were consumers of IL-7.

“To be honest, I was quite surprised that ILCs have such an effect in this model,” said lead author, Dr. Christopher Martin of The Scripps Research Institute in the US. “Relative to T-cells, there are very few ILCs in the tissues we study. So, when we were designing the initial experiments, we weren’t optimistic that we would find anything interesting.”

Another pivotal set of discoveries were made possible by the facilities and expertise unique to the Academy of Immunology and Microbiology in South Korea. The state-of-the-art germ-free mouse research facility allowed the team to show that ILCs compete for IL-7 independent of commensal bacteria.

Finally, experiments performed by Dr. Kim Kwang Soon of IBS demonstrated the molecular mechanism that explains why the ultra-rare ILCs are more effective than the abundant T-cells in consuming IL-7. This is possible because T-cells reduce the number of IL-7Rs after binding IL-7, while ILCs do not.

“The findings are not only of interest to the esoteric field of immune homeostasis, but also to the broad biological community because they are a stark reminder that life exists as a complex concert and not as a collection of various types of cells that merely just co-exist,” Surh concluded.



The article can be found at: Martin et al. (2017) Interleukin-7 Availability Is Maintained by a Hematopoietic Cytokine Sink Comprising Innate Lymphoid Cells and T Cells.

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Source: Institute for Basic Science.
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