Tolerance

[BENNY SHOMER 9238]

Jerry Woodward (woodward at seqanal.mi.uky.edu) wrote:
: Endocrine implies a systemic regulation of lymphocytes by cytokines produced at
: some distant site.  I am thinking more of local microenvironments and
: paracrine regulation of lymphocytes over short distances.  This is probably
: a better view.  In normal tissues there may be a cytokine environment
: (TGF beta or??) that tends to dampen any response even if T cells have
: receptors specific for some self antigen.  Clearly this can be overcome in many cases by hyperimmunization (such as in EAE,EAU etc).  Perhaps the cytokine
: environment in most tissues inhibits most afferent immune responses, or promotes induction of anergy, while effector cells, once produced in a local
: lymph node, are no longer susceptible.


I can't hold myself back from touching my favorite subject ;-)

A superior model (I believe...) for a microenvironmental tolerance is the 
tolerance induced by the fetus in the uterus. For many years now, people try to
prove that various cytokines (including TGF-beta) participate in the 
induction of the tolerogenic effect, that enables the embryonic immune escape.
Now, this may sound controversial to the line I was drawing earlier. Until now,
no research could establish a MAIN role for any cytokine. There were of course,
a few works, in which the balance of a certain cytokine (like IL1, CSF-1 etc.)
was disturbed by injection, and this led to abortion. But then, this is not 
surprising. It seems that the main effect is induced at the molecular/cellular
level. 
But (a graeat but...), one cann't exclude the nessecity of th evarious 
cytokines to keep the mother tolerant.

Parallel with this- It is obvious that the basic tolerogenic effects towards
self associated antigens is mainly induced by cellular interactions, but as we
learned from the case of the TGF k/o mice, and from other models, the cytokine
system is very likely to take part in the MAINTENANCE of this effect.

I wonder how these mice would have reproduced, should they have survived...


Have a nice Weekend :-)
Benny.
 **************************************************************
* Benny Shomer                                                 *
* Tel-Aviv University                                          *
* Sackler School of Medicine, Dept.of Embryology and Teratology*
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* Snail:  Ramat-Aviv , Tel-Aviv  69978 ,  Israel.              *
* E-mail :  pc386 at ccsg.tau.ac.il                               *
* Tel :  972-3-640-9238     FAX :   972-3-642-2046             *
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