Blood collection to study and modulate dendritic cell-driven T cell responses

An effective and balanced immune system is crucial for sustaining and promoting
health and longevity of people, and forms the basis for an effective fight
against infectious diseases. Aberrant immune responses are a major health
problem, as they cause chronic immune diseases. On the one hand, chronic immune
diseases can be the result of too strong inflammatory reactions (allergies and
autoimmune diseases such as arthritis and diabetes), but on the other hand the
result of too weak immune responses (cancer and uncontrolled infections).

Adaptive immune responses induced during infections and chronic immune diseases
are generally characterized by (over)activation of specific T helper cell
subsets, mainly Th1 and Th17 cells for autoimmunity, and Th2 cells for
allergies. The undisputed paradigm is that the development of these
antigen-specific effector T cells is directly controlled by dendritic cells
(DCs).

DCs are the gatekeepers of the human body. These cells are located on border
areas with the outside world, such as the skin, lungs and intestines, and are
constantly searching for danger. When these cells come into contact with
invading pathogens, they will initiate defensive reactions to eliminate the
intruder as quickly as possible. This is done by activating antigen-specific
adaptive immune responses that are characterized by the activation of T helper
cells. Depending on the pathogen, the DC will direct a T cell towards a Th1, 2,
or 17 phenotype.
However, endogenous molecules and some foreign substances (e.g. small particles
of plants, pets or microorganisms floating in the air) are not dangerous. In
that case, DCs should actually inhibit immune responses by not activating T
cells, or by inducing so-called regulatory T cells (Tregs). These Tregs can
then inhibit the activation of other T helper cells. The inhibition of immune
reactions against these innocent substances is called tolerance.

Gain a better fundamental understanding of the functioning of the human immune
system.

Our research focuses on the mechanisms involved in 2 aspects:
1. The induction of Tregs (and inhibition of Th2 cell polarization) by exposing
DCs to certain adjuvants, such as Vitamin D3.
2. The induction of Th17 cells that depends on an interaction between DCs and
cells of the innate immune system, the neutrophils.

The ultimate goal of our research is to develop disease modulating therapies by
directing DC-mediated immune responses. This is in contrast to many current
therapies, which are aimed at combating symptoms but do not address the disease
process. More fundamental knowledge of the underlying mechanisms involved in
establishing effective, tailor-made immune responses against specific pathogens
is essential for our research. In addition, we are developing strategies to
safely and effectively target immune modulators and allergens/antigens towards
DCs, with the aim of directing T cell responses in the body in the right
direction to inhibit disease activity.

Blood will be taken from healthy volunteers weekly. This blood will be used to
obtain the cells needed for our research: T cells, neutrophils, and monocytes.
Monocytes will be cultured in the laboratory into differentiated towards DCs,
which will then be used for our experiments.

These cells will be used in the lab to perform in vitro experiments. Depending
on the planned experiments, the experiments will take between 1 day (e.g.
neutrophil function study) up to a maximum of 3 weeks (study of DC-mediated T
cell polarization towards different T cell phenotypes).

At the end of these experiments, all these cells are discarded. Cells that have
been isolated from the blood, but cannot be used immediately in the experiments
(often more cells can be isolated than we can immediately use) will be stored
in liquid nitrogen. At a later stage, these cells can still be used.

Blood collection can sometimes cause mild pain or bruising. For each
participation, blood is taken once or twice, in the latter case with an
interval of 6 to 7 days. During each participation, we take a maximum of 100 mL
of blood, which will not cause any problems for adults. For comparison: the
blood bank takes 500 mL of blood at a time. In case of 2 blood samplings, we
will not take more than 20 mL during the second collection.
We estimate the load and the risks to be very limited.