In article <3pku3l$l54 at jhunix1.hcf.jhu.edu>, ejf at welchlink.uoregon.edu
(Ephraim Fuchs) wrote:
> 2) I and Polly Matzinger have shown that activated B cells expressing the
> male antigen, H-Y, induce tolerance in naive, H-Y specific T cells.
>
Three points:
Male LPS activated B cells were shown to induce male specific tolerance,
however, the mechanism towards this is totally unknown:
(I) It could have been that T cells get tolerant (deletion or anergy) by
encontering the activated B cells (thats what you term the experimental
evidence); (II) that male LPS blasts persist and
exhaust male specific T cells (but before they were very actively going,
however, I wouldnt bet for this possibility); or (III) that male LPS blasts
lack Th cell stimulatory determinants relevant in vivo (it was shown with
a CD4+ clone that on male LPS blasts is male peptide, but this was a clone
obtained by repeated stimulation and expansion; nothing to do with
in vivo !).
Th cells have been shown to be importand in induction of male specific
CTLs, therefore tolerance could well be due to lack of help.
In the transgenic H-Y specific mice it has been shown that male specific cells
divide (means they are activated !) upon injection of male cells, even
if the final outcome was tolerance due to lack of help. (Help could actually
be replaced by gene therapy of the male cells, making them to express IL-2;
this was enough to get memory cells.)
Out of this reason, its not the lack of any "alarm" factor on/within/whereelse
male LPS blasts, but lack of help, that results in tolerance after a
transient male specific CD8+ response towards LPS B cells.
Up to know, there is no need to assume that LPS B cells induce tolerance
^^^^^^^
better than any other cell. Therefore Janeway might be right.
jorg
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