Hello, my name is Bruno Silva-Santos, and I'm a professor of immunology and immuno-oncology
at the medical school at the University of Lisbon, Portugal.
I also direct a lab dedicated to studying T-cells, their development in the thymus,
and their functions in the periphery, especially in the tumor micro-environment.
Today I'll be telling you about T-cells, about what they undergo in the thymus,
and focusing on some lineage decisions that they go through,
in order to become functional and effector T-cells.
T-cells originate in the thymus, and they are educated to discriminate between
self and non-self, because ideally, you want to export from the thymus,
T-cells that recognize non-self - that is, foreign antigens such as virally-encoded antigens, tumor
antigens, et cetera - and that are tolerant to self-antigens, namely, the proteins our tissues express.
For this, the thymus has a particular structure, with very well-defined areas which we call the cortex
and the medulla, and these harbor different populations of thymic epithelial cells that we call
CTECs and mTECs, depending on where they are located.
These thymic epithelial cells have a lot of interesting characteristics,
including (in the medulla) expressing the transcription factor AIRE that is
a key molecular switch for tolerance.
That is, it is capable of inducing the expression of tissue-specific antigens such as insulin
(for instance) associated with the pancreas, or myelin associated with the CNS, so that
T-cells being educated in the thymus can be tolerant to these peripheral antigens.
T-cell receptors, which are the hallmark of T-cells, are tested for their affinity to self-peptides,
to peptides derived from these self-proteins (as I mentioned), which leads to only T-cells that have
T-cell receptors of intermediate affinity being exported to the periphery.
That's the aim, that the vast majority of T-cells that go to the periphery are specific for foreign antigens
to which they have a medium affinity.
Self-antigens to which they have very strong affinity induce what we call 'negative selection',
that is the deletion of these T-cells in the thymus so that they never reach the periphery,
and this avoids autoimmunity (as you can imagine).
Although this process would be ideal, we do know that all of us have some auto-reactive T-cells in the
periphery that need to be controlled by peripheral mechanisms in order to avoid autoimmunity.
When these mechanisms fail, then autoimmunity appears,
and you'll have lectures on autoimmune diseases.
T-cell commitment is to one of the two major lineages of T cells, the so-called 'helper'
and 'cytotoxic' T-cells.
CD4⁺ T-cells are associated with helper functions, producing cytokines that help other immune cells
to be activated, or displaying regulatory functions that orchestrate the function of the other immune
cells; whereas CD8⁺ T-cells are the cytotoxic cells, the ones endowed with a capacity to eliminate
virally-infected or tumor cells, for instance.
Today we'll focus on the several lineage decisions that T-cells go through in the thymus.