Tolerance vs Autoimmunity

Thomas C.M. Tung tct8 at namaste.cc.columbia.edu
Mon Nov 14 12:22:42 EST 1994


I was hoping that some of the scientists on this newsgroup can answer a 
question I have regarding neo-class II MHC expression and its relative
role in autoimmunity and induction of peripheral tolerance.

In my immunology course, one mechanism that was cited for the induction
of peripheral tolerance was the stimulation of TCR-CD4 by Class II MHC
and self-peptides in the absence of the costimulatory CD28-B7 interaction,
resulting in T-cell anergy.  Supposedly, this prevents cells other than
professional APCs from activating T Cells, i.e. cells presenting peptides
on Class II MHC w/o B7 induce anergy.

Yet, one mechanism that is frequently given for autoimmunity is neo-class
II expression on epithelial cell lines with presentation of self antigens
that T cells were not tolerized to in the thymus.  This seems to be 
inconsistent with the earlier theory on tolerance induction.  

How are these divergent purposes served by the same mechanism?  
It seems like g-IF, which induces neo-class II expression would also have
to induce B7 expression too in order to cause autoimmunity -- is this 
observed experimentally?

Thanks
Tom



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