HIV and TCell Numbers/Memory

Jorg Kirberg kirberg at bii.ch
Mon Feb 27 13:11:52 EST 1995


In article <leew.50.000CF473 at wadsworth.org>, leew at wadsworth.org (Bill Lee)
wrote:


> 
> If a limited expansion (and subsequent selection) were true, what does this 
> say about Ag stimulation vis a vis a homeostatic mechanism for obtaining 
> "normal" T cell numbers?  To account for that high degree of expansion, 
> wouldn't the responding cell have to proliferate much more vigorously to a 
> given Ag than it normally would in a normal mouse, to account for the 
> increased cellularity in the nude spleen?
> 

Hi Bill,

one point I deleted as citation from above but would like to adress briefly:

I think the experiments, showing that expansion in an "empty" host as the
nu/nu mouse is antigen mediated, have been done (Rocha, B., von Boehmer, H.
(1991) Peripheral Selection of the T Cell Repertoire. Science  251, 1225-1228).
(of corse my view is biased as I belong to the group of von Boehmer, sorry).

Even for me it is "strange" that so many cells look responding to
unknown antigens. However, this statement cant be made, as the frequency
of later proliferating cells in the inocculum is unknown. Therefore it might
be interesting to find out if this repertoire is oligoclonal. I do not know
of any study that has been adressing this (but maybe I simply missed it).

Up to now one might speculate: Maybe the transgenic receptor used is of
particular low affinity (e.g. it is CD8 dependent). In the antigen free host
it might never be stimulated enough to allow proliferation.
But other T cells might have a higher affinity, good enough to get slowly
proliferating just by the MHC presenting anything. E.g. in one of these
recent Immunity papers where transferred TCR transgenic CD4 T cells were
immunized, the transgenic CD4 cells expanded slowly. Either these cells were
crossreactive enough to allow their expansion without antigen; the situation
with CD4 cells is different as to the CD8 studies mentioned above; or more
simple, as those latter studies did not use the CD4 transgenic cells from
Rag-1or2-/- mice these cells had additional TCR genes rearranged, expressing
an additional TCR by which they got stimulated (actually this would even
question if the cells used were real naive cells).

Anyhow the point you made is quite interesting: what actually determines
when the mouse is full??? Maybe reactive cells are allowed to proliferate
longer in the "empty" mouse, thereby allowing some homeostasis. Up to
know I think it is not known what actually limits the clonal size of a cell
in a mouse. If you repeatedly immunize the frequency of reactive cells does
not go to 100 percent. Somehow its limited.
Maybe some mouse modells of "unlimited" expansion (lpr and gld) will allow
some answers (it seems to be a hot topic; at JAX there is a long waiting
list for these strains). It could be quite simple: activated T cells express
the FasL and Fas: if the density of cells gets to high they just kill each
other via Fas. (Still this is no real answer for the limited clonal size).

Maybe those labs doing the experiments with the lpr or gld mice should tell
their results ?

jorg

-- 
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Joerg Kirberg                     EMAIL: kirberg at bii.ch
Basel Institute for Immunology    FAX:   41-61-605 13 72
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