Controlling cell population sizes: When is enough?

Researchers at the University of Basel have discovered an intracellular mechanism that controls the appropriate number of T cells in the body and thus ensures the proper functioning of the immune system. This mechanism has also been found in slime molds, suggesting that this regulation of cell density is evolutionarily conserved.

The research is published in Scientific Signaling.

Our immune system, which is responsible for controlling attacks from viruses, bacteria, parasites, and also preventing the appearance of cancer cells, is made up of multiple types of cells. There are billions of these immune system cells in our body, including T lymphocytes, or T cells for short.

T cells are produced in the bone marrow, selected in the thymus gland and are essential for the proper functioning of our immune system. While enough T cells must be present at all times, the body must also ensure that they do not exceed a certain density. But how does the immune system recognize whether there are the right number of T cells in circulation?

Coronin proteins control T cell population size

The research team led by Prof. Dr. Jean Pieters at the Biozentrum of the University of Basel has now been able to reveal the cell’s own mechanism that regulates the size of the T cell population. Their previous work, as well as that of other groups, already showed that a protein called coronin 1 plays an important role in the survival of T cells in the body.

In the new paper, the researchers report that when the number of T cells increases, the expression of the protein coronin 1, which is already among the most abundant proteins in T cells, increases further. This promotes the survival of T-lymphocytes and thus ensures a sufficient size of their population.

But how does the system decide when enough is enough? The researchers discovered that coronin 1 production stops when the upper limit of T-cell density is reached. As a result, survival signals for cells otherwise activated by coronin 1 are missing.

“Cells begin to die and the density of the T-cell population decreases again,” explains Tohnyui Ndinyanka Fabrice, first author of the study. “It took a long time to visualize this process. But once we got it, our observation was like watching a disaster movie: If the cells were too crowded, a massive death within clusters of cells started.”

An evolutionarily conserved mechanism

Interestingly, the research results also showed that the regulation of cell population by coronin is also found in amoebae (slime molds), which go through both unicellular and multicellular stages. This finding opens exciting avenues for future research.

“Members of the coronin protein family are highly conserved and widely expressed across the eukaryotic kingdom,” says Professor Jean Pieters. “Future work could potentially shed light on whether coronin-dependent regulation of the respective populations of T cells and slime molds also works in other systems.”