In article <3pcoc4$pjb at jhunix1.hcf.jhu.edu>, Chris Thoburn (cthoburn at welchlink.welch.jhu.edu) writes:
> In article <1995May16.135540.1 at ania.path.ox.ac.uk>, macpherson at molbiol.ox.ac.uk> writes:
>>>>>John, Undoubtedly whole proteins can get into the blood from the gut in small
>>amounts and do not seem to be immunogenic, but, if soluble proteins, carefully
>>freed from complexes, aggregates and denatured molecules are injected IV, they
>>are often tolerogenic, despite peptides from them being present as immunogenic
>>complexes with MHC on spenic dendritic cells (Inaba & Steinman). Similarly,
>>we have shown that after feeding OVA or KLH to rats, DC in the intestinal wall
>>acquire antigen-derived peptides and can present them to sensitized T cells
>>"in vitro" and can sensitize naive T cells "in vivo" (Liu & MacPherson). We
>>have always puzzled about this anomaly of mature, immunostimulatory DC
>>expressing antigenic peptides but not causing sensitization, and this is where
>>Polly Matzinger's ideas make sense - if the DC require some extra "danger"
>>signal to enable them to activate a resting T cell, all is well (our "in
>>vitro" manipulations of DC may be all that is required to "activate" them).
>>We do not however have any idea what activation of a DC means! Our
>>lymph-borne DC express high levels of B7 when we collect them.
>>>>Gordon MacPherson
>>macpherson at molbiol.ox.ac.uk>> When you feed OVA or KLH to these rats, are the DC cells the only antigen
> presenting cells involoved or could perhaps another APC (for instance B cells)
> also present the antigen? If this is true could then the non-DC APC be
> responsible for inducing tolerance and the DC would not require a 'danger'
> signal?
>>> Chris Thobur
Chris,
I may have screwed up my reply so here goes again.
We cannot exclude B cells from acting as APC and tolerizing to oral
antigens, but there is an experiment waiting to be done (it amy have been done
but I have not seen the results). Does oral antigen tolerize in B cell
deficient (Mu chain KO's or T cell-reconstituted SCIDs ? If B cells acquiring
antigen in nodes tolerize, why do contact sensitizers (eg DNFB) applied to
skin not tolerize? Large amounts of antigen arrive at the node via afferent
lymph long before migrating Langerhans cells get there.
It is of course possible that B cell APC activity and lack of
activation of DC both play a role.
Gordon MacPherson
