Billions of viruses and new CD4+ cells daily
JAF at UNCVX1.OIT.UNC.EDU
JAF at UNCVX1.OIT.UNC.EDU
Sat Mar 18 08:55:05 EST 1995
I heard a nice talk by Lishan (sp?) Su from Systemics last week which
gave pretty good evidence in scid hu mice that the presecne of HIV
infected cells in the thymus causes a selective induction of apoptosis in
UNINFECTED CD4 bearing cells in the thymus. If this is really true it
accounts for the ability of HIV to deplete the CD4 pool even when most of
the cells are not infected.
On Fri, 10 Feb 1995, Dr M.R. Clark wrote:
> In article <21211 at sci.med.aids>, Ian A. York <york at mbcrr.harvard.edu> wrote:
> > One very obvious question that arises from the new findings is,
> >why do CD4 cells eventually crash? Early in the disease (it's now
> >appropriate to call it a disease even early on, rather than just 'HIV
> >infection') the dying CD4's are replaced to reach a stready-state level.
> >Later, there is a steady decline. It's remarkable that this pattern is
> >followed. If you think about it, a steady gradual decline is just about
> >the least likely scenario that could happen - it means that there is a
> >replacement of all but a tiny part of the loss. I can easily picture
> >mechanisms to explain either a total crash or steady state replacement -
> >I have a harder time with a mechanism that would consistently replace
> >(say) 1,000,000,000 instead of 1,250,000,000 - or whatever it works out to.
> What about the following idea? What if the homeostatic mechanism for
> maintainence of CD4 cells acts on the sum total of CD4+other cell types
> eg CD4 & CD8 or even CD4, CD8 and NK. If the virus depletes one subpopulation
> at a faster rate than another or one subpopulation replenishes at a faster
> rate than another then gradually you would see a decline in CD4 cells. In
> addition this would be accompanied by a change in the CD4/CD8 ratio or
> even the CD4/(CD8+NK) ratio.
> One observation I can use to back this up is from the experience of an
> ex colleague of mine Steve Cobbold. In his experiments where he depleted
> mice of CD4 or CD8 cells with antibodies he found that the other population
> expanded to fill the gap. Even over long periods of time most mice did not
> recover "normal ratios". Also mice depleted of CD4 and CD8 seemed to fill up
> with larger numbers oflarge granular lymphocytes.
> o/ \\ // || ,_ o Mike Clark, mrc7 at cus.cam.ac.uk
> <\__,\\ // __o || / /\, Cambridge University, Dept. Pathology
> "> || _`\<,_ // \\ \> | "an antibody engineer who prefers the
> ` || (_)/ (_) // \\ \_ mountains"
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