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màj 23/07/98 |
Report
by P. Jourdan on the following session :
| Vendredi
13 Février 1988 |
Présentateurs/Speakers
|
Modérateurs
|
Experts
|
14h00-15h00
|
Allergie - Lymphocytes
|
H.
Yssel (Montpellier)
M.
Pretolani (Paris)
Discussion
|
15'
15' 30'
|
C.
Jorgensen (Montpellier)
A. Magnan (Marseille)
|
S.T.
Holgate (Southampton, UK)
M. Gaga (Grèce)
|
Dr Hans Yssel has made
an overview of the recent publications on T helper 1(Th1)
and Th2 in the context of allergic asthma. Asthma is a
reaction of hypersensitivity characterized by an
inflammation of the lung tissue. A number of studies have
established that CD4 T cells are
involved in the pathogenesis of asthma. Th1 produce
preferentially IFN-g
and IL-2 and are implicated in inflammatory reactions and
cell-mediated immunity, whereas Th2 produce IL-4 and IL-5
and are involved inanti-inflammatory reactions and
humoral immunity. The differenciation of Tcells into Th1
or Th2 is largely dependent on the regulatory effects of
certain cytokines such as IFN-g, IL-12 and IL-4 which promote or
suppress the growth of one or the otherof these subsets.
The Th2-type cytokines promote B cell switching to IgE
production and activation of eosinophils and neutrophils
wich are found in the inflammatory allergic reaction, and
Th1 cells are present at the sites of allergic
inflammation. Questions which are presently addressed are
what kind of receptors do these cells express and what
makes them to home certain types of tissues. Recent
studies have clearly demonstrated that T helper subsets
could be characterized by the differential expression of
certain cytokine and chemokine receptors. Human Th0 and
Th2 clones maintain the expression of transcripts and
protein forms of the IFN-g receptor
b-chain (IFN-gRb),
whereas polarized human Th1 clones loss this expression
upon their differentiation from precursors. At the
opposite, the IL-12 receptor b-chain
(IL-12Rb2) is
preferentially expressed by Th1 mouse and human T cells
clones. Thedifferential expression of chemokine receptors
by Th1 and Th2 cells is under investigations. It has been
shown by different groups that chemokine receptors CXCR3
and CCR5 are preferentially expressed by Th1 clones,
whereas CCR3 and CCR4 would rather characterize Th2
clones. Although the regulation of these chemokine
receptors is still unclear, it has been demonstrated that
CCR3 expression decreased as a result of T cell
activation.
|
During the discussion severals aspect of T cell
subsetregulation were adressed.
At first, Dr Gaga asked whether the loss of cytokine receptors
during differenciation lead to a strong polarized phenotype Th1or
Th2. According to Dr Yssel, the IFN-g
acts as a strong inhibitory factor only on Th2 cells, while IL-12
has a positive effect on Th1 but not on Th2. This observations
correlate with the demonstration of absence of IFN-gRb and IL-12Rb2
on human Th1 and Th2 clones, respectively. But Dr Yssel
emphasized the crucial point that even human clones seem to be
polarized, and in contrast to observation in mice, the polarized
human populations in vivo are certainly quite plastic.
The other questions concerned the kinetics of receptor
expression and the involvement of Th subset in the development of
disease. Although such populations are quite difficult to study in
vivo for human diseases, it exists some model like leprosis
in wich a Th1 response is first observed, then a Th2 response,
which could limit the domages done by Th1, appears.
Dr Maria Petrolani has presented the recent
results obtained by her group concerning the role of CD4+ T cells
gd+ in mice in the allergic
airway inflammation disease. A number of studies about the
inflammation disorders have focused on the T cell subsets
characterised on the basis of their cytokines profil (Th0, Th1
and Th2 subsets). However T cells gd+
residing primarily in epithelia-rich tissues are claimed to play
a role in the emergence or resolution of inflammatory immune
process. The question wich is presently adressed is what
specifically role play this population in epithelia-rich tissues
in mice. Transgenic Balb/c knock out for TCRgd (gd-)
mice were used. Mice systematically sensitized with ovalbumin
(OVA) were challenged with OVA via intranasal route and studied
for the proteins secretion and cellular recruitment in tissues.
An important decrease in level of IL-5 and a very low numberof
eosinophils, CD4+ and CD8+ T cells were observed after OVA
challenge in broncho-alveolar lavage fluid (BALF) for gd- T cell deficient mice compare
to normal mice. However no change in the amounts of IL-10 and IgG
was detected.
The discussion has focused mainly on the problem of animal
model asking questions whether the animal model used in this
study is correct compare with chronic asthmatic patient and
whether it is possible to obtain model close to human disease.
According to Maria Petrolani "the animal model used in this
study does not reproduce the chronicity, but it reproduces an
acute phenomena".Thus it provides an elegant model to study
acute phenomena as well as bronchial hyperreactivity (BHR).
Moreover, one problem with animal models in asthma is that mice
respond poorly in the airways. Thus to get BHR, fibrosis or
chronic modification in airways forms, mice have to be challenged
for many times.Thus "the right model does not exist".
This opinion is shared with Pr Aubier: "It is difficult to
extrapolate from animal model to human". However Pr Magnan
said "each animal model gives some key on the mechanim of
one or several groups but certainly not all the atopic
populations". According to Pr Nijkamp "Animal model
does not necessarily have to look alike as human asthmatics
patients, because what we need to learn from animal models is
basically new concept like Th1 and Th2 model".
. 
Enfumosa Congrès Conçue et réalisée par: Michel Godard (at) Top
Date de création: 12 Février 1998 -Dernière mise à jour: 23/07/98
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