Let’s just spend a couple of moments to look at gamma-delta
(γδ) T-cells, and exactly what they do and what they are.
They appear to have a distinct role that is
complementary to that of the alpha-beta (αβ) T-cells.
They comprise less than
five percent of the T-cells.
So they’re very much a
minority population of T-cells.
And they’re present mostly in the gut mucosa,
in the skin, in the lungs and in the uterus.
And they can directly recognize microbial pathogens,
and also damaged or stressed host cells.
In other words, our own cells that are damaged
due to infection or other types of pathology.
To give you just a couple of examples of the
recognition that can occur by γδ T-cells.
You can have direct recognition of
phosphoantigens from Mycobacterium tuberculosis,
from Plasmodium malariae without any
requirement for antigen processing whatsoever.
And there can be direct recognition of the
MHC-like non-peptide-binding molecules,
MICA and MICB, or of CD1 irrespective of
any lipoprotein or glycolipid antigen.
So they can recognize structures that are
coming from foreign pathogens, but they can also
recognize our own molecules that are upregulated
in response to stress or other events.
Here’s the structure of the T-cell
receptor on the surface of a T-lymphocyte.
It’s a heterodimer,
consists of two chains.
And here we can see the
αβ T-cell receptor.
The γδ T-cell receptor
looks almost identical.
In both cases, the two chains of the T-cell
receptor are linked together by a disulfide bond.
There are transmembrane segments associated
with both chains of the T-cell receptor.
Each chain is folded into two domains; a Variable
domain which is stabilized by an intra-chain
disulfide bond, and a Constant domain also
stabilized by an intra-chain disulfide bond.
Looking at exactly how the T-cell receptor
interacts with peptide MHC; at the
top of this diagram, we can see the two
Variable domains of the T-cell receptor.
Underneath is the MHC Class I α-chain.
This is associated
And then sitting between the α-helices of the
MHC Class I α-chain is the antigenic peptide.
And this is making contact not only with the
MHC but also with the hypervariable or CDR
regions of both the α-chain and the β-chain
of the T-cell receptor Variable regions.
αβ T-cells, are not all the same.
There’s a variety of
different types of αβ T-cells.
So let us look at the different types.
Well, there are ones that have CD4 on their cell surface
and there are others that have CD8 on their cell surface.
So that’s one distinction.
Within the CD4+ αβ T-cells, there are
a number of subpopulations - Th1,
Th2, Th17, T-follicular helper and
T-regulatory cells amongst others.
These are the most important, or at least the
best characterized at this point in time.
They can be distinguished by a
number of different features.
So if we look at the transcription factors that
are expressed in the nucleus of these different
types of T-cell, we see that Th1 cells express
the transcription factors T-bet and STAT4.
They produce a variety of different cytokines - gamma
interferon, interleukin-2, tumor necrosis factor beta.
These are typical cytokines
that are produced by Th1 cells.
And in fact, the first distinction
of these different types of helper
T-cells was based upon the particular
cytokines that they produced.
The primary function of Th1 cells is to help
cytotoxic T-lymphocytes and to help macrophages.
Although, they can also help
some B-cells to produce antibody.
Importantly, they can inhibit
the activity of Th2 cells.
Turning now to Th2 cells, they express the
transcription factors GATA3 and STAT6 in their nucleus.
They produce the cytokines
interleukin-4, IL-5, IL-6 and IL-13.
And their primary function
is to help B-cells.
Importantly, just like Th1 cells can inhibit
Th2 cells, so Th2 cells can inhibit Th1 cells.
So these two populations, Th1 and Th2, at least to some
extent are mutually antagonistic towards each other.
Th17 cells express the transcription
factor RORγt in the nucleus.
And as their name suggests, they produce interleukin-17,
amongst other cytokines such as interleukin-22.
And these cells are really
specialized to promote inflammation.
T-follicular helper cells are cells that
are found in the germinal centers of
secondary lymphoid tissues where they
assist in the activation of B-lymphocytes.
They express the
transcription factor Bcl-6.
And they produce cytokines such
as interleukin-21 and ICOS.
And as I’ve already mentioned, their
function is to help germinal center B-cells.
So those four cell types all enhance immune
responses, they help immune responses.
In contrast, T-regulatory cells
suppress immune responses.
And they express the transcription
factor Foxp3 in their nucleus,
very characteristic transcription factor of regulatory T-cells.
The cytokines they produce tend to be cytokines
that overall have immunosuppressive activity.
Cytokines such as transforming growth factor
beta, interleukin-10 and interleukin-35.
And again as I’ve already mentioned, the primary
function of T-regs is to suppress immune responses.
So those are different types of CD4+ αβ T-cells.
What about the CD8s?
Well, these are generally
And they express in their nucleus,
the transcription factor RUNX3.
They function by producing molecules
such as perforin, granzymes,
Fas ligand, but they can also produce a variety of cytokines.
And their role is to
kill infected cells.