The path to becoming a scientist takes a lot of work. There are many years of studies, papers to read, hypotheses to formulate, and experiments to do. Does it sound hard to you? Well… you have no idea the sort of education our immune cells have achieved to be successful at keeping us healthy.
Today, we will focus on the education of our famous T cells. Although the curriculum that these immune cells undergo has only two main topics: (1) “function well” and (2) “don’t kill your friends,” the process involving this “education” is very intricate and extremely beautiful.
Nevertheless, there are still plenty of open questions (with more coming every day) about how exactly our immune cells can do this. But for now, let’s dive deep into what is already known. As always, get ready to be amazed by the beauty of our immune system.
If you read a few of my old posts, you know that T cells perform crucial jobs, such as helping during an immune response and killing infected and cancerous cells. But for them to become these incredible immune soldiers, they need to undergo some arduous education.
The immune system university
T cells develop in one of the most underrated organs: the thymus. This organ is located just above the heart and acts as one of the immune system’s “universities.” (The idea of the thymus being a “university” comes from the book Immune: A Journey Into the Mysterious System by Philipp Dettmer.)
The T cell university, created with BioRender
One of this organ’s coolest and most important features is that it is VERY “well-designed.” The architecture of the thymus plays a huge role in how well the cells move, learn, and ultimately succeed in keeping us alive.
At a very early stage of a T-cell-to-be, an immature immune cell will enter the thymus and receive a variety of important information, which allows it to develop and mature in this organ. During development, a single immature cell that enters the thymus can undergo up to 20 serial divisions, which means that a single cell can proliferate enough to give rise to one MILLION cells! [1] (If you want to know more about T cell development, check out this post)
At some point during this process, our T-cell-to-be is required to pass an “exam” composed of two simple but crucial questions. The first question is, “Are you a functional T cell?” If the answer is yes, this developing T cell-to-be must answer a second question: “Are you going to kill enemies or friends?”
In the immune system view, “enemies” are composed of pathogens (microorganisms that cause diseases) or cancer cells (mutated cells). “Friends” are any healthy cells in our bodies, such as cells that compose our skin, pancreas, heart, thyroid, etc. So, it is easy to see why answering this second “question” correctly is essential in helping avoid the development of autoimmune diseases (which is when our immune system attack our healthy organs).
The surviving immune soldiers
Although this might sound funny, this analogy is not too far from the reality of what happens in the thymus. Passing these two tests (also known as positive and negative selection) is crucial as they allow us to have an immune system composed of functional and tolerant T cells (i.e. attack foes, not friends).
Easy, right?! Well… not so fast. Some studies suggest that about 95% of the developing T cells do not actually pass one of these tests, and the penalty for this is as harsh as it can be: death [2]. Yes, a vast majority of our “aspiring” T cells will die during their development. But this is a small price to pay to have only great immune soldiers!
So next time you complain about your classes or exams, remember that your immune cells are also doing their education, day and night, with a penalty much higher than a bad grade.
T cell education is a passion of mine, so if you want to know more, follow @ImmunoThoughts so you do not miss any further posts!
Keep asking questions and seeking answers!
From your immunologist – in training,
Stefanie Valbon, MSc, PhD candidate
[1] Porritt, H.E. et al. Heterogeneity among DN1 prothymocytes reveals multiple progenitors with different capacities to generate T cell and non-T cell lineages. Immunity 20, 735-745 (2004).
[2] This, S., Rogers, D., Gauthier, È. M., Mandl, J. N. & Melichar, H. J. What’s self got to do with it: Sources of heterogeneity among naive T cells. Semin. Immunol. 65, 101702 (2023).
