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Opinions on whether TH1 and TH2 cell types originate from TH0

Thierry Sornasse tsornas at dbmdec5.ulb.ac.be
Wed Mar 9 11:37:41 EST 1994

Hi Immunonetters,

The discrimination between Th1 and Th2 phenotypes was established from data about
T cell clones derived from mice. With this background, it is possible to
characterize individual cells. Although, if you look in vivo, the image you will
get is quite more confuse. Moreover, the studies made in human suggest strongly
that the simple scheme of Th1/Th2 is rather difficult to apply. 
On the other hand, if you focus your attention on global response and not on
single cells, I think that it is possible to characterize either Th1 like
response or Th2 like response. In each case the cytokines and the effectors
implied in hte response will be different, altho!ugh  with some overlapping. 
I think that in the scope of therapy, the global evaluation of Th1/Th2 balance 
should lead to better results than the fine description of individual clones. 
I think that is one of the reason why immunologist look only to specific
cytokines like IL4,IL10,IL2 and IFNg. The detection of these cytokines is
sufficient to predict with a good confidence the type of response studied.

About the hypothesis that Th1 and Th2 are the result of the differentiation of
Th0, I am convince that is the best way to describe the regulation of the immune
response with the present background. 
This hypothesis fit perfectly in vitro experiments (patterns of cytokines
secreted by T cells which have been activated once or twice).
The paper of the team of A. O'Garra about the role of macrophages and dendritic 
cells in the differentiation of Th1 clones from naive T cells confirms this
hypothesis. In fact, you need both DC and Mac to get a optimal Th1
differentiation. DC activate naive T cells but do not trigger the differentiation
of Th1, while Mac do not activate naive T cells but trigger the differentiation
of Th1 by secreting IL12. In other words, DC would allow the activation of Th0
and Mac would allow the differentiation of activated Th0 to Th1.
In vivo, the situation seems to be more complicated. If you consider an adult
human, his immune system is not naive. Thus, there could be some memory T cells
that are already shifted to Th1 or to Th2.

In conclusion, I could say that the relevance of the Th1/Th2 discrimination
depends on the scale at which you study the immune system: the model fits well to
a global scale but the at the clonal scale the model is practically useless.

Best regards

/              T H I E R R Y              S O R N A S S E
/                  Laboratoire de Physiologie Animale 
/      Universite Libre de Bruxelles / Free University of Brussels
/              Rue des Chevaux, 67.   1640  Rhode-St-Genese 
/                              B E L G I U M
/  Phone: 32.2.6509850                               Fax: 32.2.6509840
/                        tsornas at dbmdec5.ulb.ac.be



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