Tolerance

Jeremy John Ahouse ahouse at hydra.rose.brandeis.edu
Wed Jul 14 10:09:50 EST 1993


In article <CA4KtG.Kn1 at news.cis.umn.edu>, shiv at hiv.med.umn.edu (Shiv A.
Prasad) wrote:
> 
> In article <CA26DH.6Fy at ms.uky.edu> woodward at seqanal.mi.uky.edu (Jerry Woodward) writes:
> >	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?
> >
> 
> Clearly we all have a number of self-reactive clones, but I don't think it's
> fair to ascribe all tolerance to cytokine effects.  Clonal deletion clearly
> plays a role in self tolerance in mice :-) Clonal anergy and clonal ignorance
> may also be important players.  Cytokine effects may be more local, eg the
> ACAID phenomenon in the eye.  It's difficult to envision cytokines playing
> a role in systemic tolerance, or else we'd never gain immunity against 
> infectious agents.  
> 
   It is worrying (as Shiv points out) to shift responsibility for
recognition to parts of the system that seem to be more generic (like
cytokines).  Jerry's example does seem to indicate a role for system wide
down regulation.  Maybe lots of low affinity (=? multispicificity) receptor
bearing cells are kept in check somehow by numbers and cytokine levels but
are given a chance for clonal expansion and recruitment in the TGFbeta
minus animals and so we "see" these clones in this case.  hmmm...


        :::::::::::::::::::::::::::::::::::::::::::
        Jeremy John Ahouse
        Center for Complex Systems and Biology Dept
        Brandeis University
        Waltham, MA 02254-9110
        (617) 736-4954
        email: ahouse at hydra.rose.brandeis.edu
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