Jeremy John Ahouse ahouse at
Wed Jul 14 10:09:50 EST 1993

In article <CA4KtG.Kn1 at>, shiv at (Shiv A.
Prasad) wrote:
> In article <CA26DH.6Fy at> woodward at (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
        Mail from Mac by Eudora 1.3.1 - RIPEM accepted

More information about the Immuno mailing list