Tolerance

Jeff Tokazewski jeff at mirth.Princeton.EDU
Mon Jul 12 13:36:48 EST 1993


In article <CA26DH.6Fy at ms.uky.edu>, woodward at seqanal.mi.uky.edu (Jerry Woodward) writes:
|> I'm new to the bionet.immunology scene.  Since there was nothing to read, 
|> I decided to post a message and to see if there is anyone out there interested.
|> Perhaps we need an alternative way of thinking about the immune response.
|> We normally think of a response as an activation event to a foreign antigen. 
|> Perhaps it is better to see it as an absence of a toleragenic signal.  In 
|> other words, tolerance is the default pathway.  There is no such thing as a 
|> "self" or a "non self" antigen.  It is simply the manner in which it is 
|> presented to the immune system.  This is probably controled to a large degree
|> by a complex interaction of cytokines.  

I agree that cytokines play a great role in modifying immunological activity in
individuals down to the cellular level, but I think it must be stressed that 
the thymus and other primary maturation sites of T and B cells are important in
suppressing those clones that are specific for self antigens.  Clearly, the 
body produces clones that are specific for self antigens, but these clones are
(in most situations) carefully selected in either a positive or negative manner
by the thymus.  

|> 	The TGFbeta knockout mouse is a case in point.  If T cell receptor 
|> repertoire is so important, why did this mouse come down with massive,
|> multifocal autoimmunity?  This suggests that we all have a very great number
|> of self reactive clones, but that self tolerance is maintained by cytokines
|> such as TGFbeta.  
|> 	I could go on for a while-- Is there any discussion?
|> 

TGFbeta knockout may have been responsible for the multifocal autoimmunity as described in the study, but it is not the absence of the cytokine, but rather
the cytokine's effect on the thymus in maintaining control over self-binding
clones that produced the above effect.



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