In article <kirberg-2302950907380001 at seven.bii.ch> kirberg at bii.ch (Jorg Kirberg) writes:
>From: kirberg at bii.ch (Jorg Kirberg)
>Subject: Re: HIV and TCell Numbers/Memory
>Date: Thu, 23 Feb 1995 08:07:38 GMT
>In article <leew.49.000D1EBC at wadsworth.org>, leew at wadsworth.org (Bill Lee)
>wrote:
>> In article <3icu9c$1vd at netnews.upenn.edu> David Peritt
><Peritt_d at a1.mscf.upenn.edu> writes:
>><snip>
>> Regardless
>> of which population was transferred the phenotype was always that of a memory
>> cell (Bell and Sparshott expts notwithstanding, although I think that data
>> comes from long-term (1-year) transfers). This is interesting as the change
>> in virgin phenotype must not be due to activation by Ag but due to expansion
> ^^^^^^^^^^
>> as part of homeostasis.
>Hi Bill,
>could you give any reason why the expansion must not be Ag mediated ?
>The specificity of the cells is unknown, they are of naive phenotype
>before transfer and gain the memory phenotype. Therefore, why shouldnt
>Ag be responsible for an enormous expansion of certain cells (maybe of
>limited clonal size) whereas the others just stay around, but will be
>difficult to find as outcompeted in cell numbers by the expanding
>ones.
>jorg
I think that's a reasonable explanation, although my initial feeling was that
the failure to find any virgin cells 1 month post-transfer reflected
polyclonal expansion. Certainly, the range of environmental Ags which would
drive proliferation of all cells wouln't be that broad. Alternative
explanations, as you correctly point out, would take into account dilution of
virgin cells by the tremendously expanded population or perhaps death of
nonstimulated cells leading to selection of the activated population. Off
the top of my head I would think that this may be testable as you might
expect that (or be lucky enough to find) that the expanded pupolation is
oligoclonal. If this were so an analysis of TcR repertoires might be
feasible.
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?
Bill
