In order to activate lymphocytes, stimulation through
the antigen receptor alone is not sufficient.
You need what is referred
to as co-stimulation.
So here we have a T-cell, that’s a naïve
T-cell, it hasn’t encountered antigen before.
Its T-cell receptor is recognizing peptide MHC on the surface
of an antigen presenting cell, like a dendritic cell.
So this APC (antigen presenting cell) is showing peptide
together with MHC to the T-cell receptor on the naïve T-cell.
But actually nothing’s happening, because that’s
the only signal that the T-cell is getting.
And the result, if there is stimulation only
through the antigen receptor, will be that there
is actually functional inactivation of the
T-cell; a process that is referred to as anergy.
So there’s no response and we have
a form of immunological tolerance.
And this process of inactivating T-cells is very useful
in preventing unwanted reactivity against self antigens.
However, in the context of infection,
dendritic cells become activated
by the Pathogen-Associated Molecular
Patterns present on microbes.
And part of that activation of the dendritic cell,
causes them to increase the expression of co-stimulatory
molecules like the B7 molecules and also to release
co-stimulatory cytokines such as interleukin-12.
So in the context of infection, dendritic
cells up-regulate the co-stimulatory
molecules and cytokines that are required for T-cell activation.
This will cause T-cells to themselves produce
cytokines such as interleukin-2, and this
will feed back onto the interleukin-2 receptor
which is also expressed on these T-cells.
And you’ll get extensive proliferation
following activation of these T-cells, the
development of effector T-cells, T-cell
survival, proliferation and differentiation.
The CD80 and CD86 B7 molecules are not the only
molecules that are involved in co-stimulation.
So here we have an example of a dendritic cell that
is expressing the molecule CD40 on its cell surface.
When the T-cell is stimulated by the
dendritic cell, one of the things
that can happen is that CD40 ligand
becomes expressed on the T-cell.
And the CD40 ligand binds to
the CD40 on the dendritic cell.
And this can lead the dendritic
cell to express higher levels of B7.
So there’s a feedback loop whereby interaction of CD40
ligand on the T-cell with CD40 on the dendritic cell, causes
the dendritic cell to increase its expression of the B7
molecule - CD80 and CD86; and also to release cytokines.
So the activated dendritic cells stimulate
T-cell proliferation and differentiation.
They have on their cell surface all
the molecules now required to do that.
They have MHC and peptide that can
stimulate the T-cell receptor.
They have CD40 that stimulates
through CD40 ligand.
And crucially, they have those all
important B7 molecules that can
co-stimulate via the CD28 molecule
on the surface of the T-lymphocyte.
And also they’re producing cytokines
that further aid in the activation.
So you have enhanced T-cell proliferation and
differentiation resulting from these co-stimulatory signals.