re aids isnt a cd4 disease....

Ralph M Bernstein ralph at ccit.arizona.edu
Mon Mar 27 09:52:22 EST 1995


Ok, 
previously Christopher J. Savoie posted about the idea that cd4 cd8 dp are
the possible targets for hiv/cd4 mediated integration..

    these are interesting thoughts christopher, and i buy most 
of them, but i wonder why a cd4 "pipe line" effect _doesnt_ occur?
and especially when a means of the virus killing cells 
hasn't been especially clearly established, how can we postulate 
that the cd8s are taking the worst beating, and especially
since the idea that new cd4 sp are more easily apoptosed, and/or
sensitive to self-elimination.  afterall, this only makes
sense, :you want the cells that can help "control"/modulate 
an immune response to be under a more finely tuned system of
control.  
    i buy your idea that there isnt a noticable increase
of infection in the cd8 compart, because of apoptotic loss,
but the cd4 comp should be much more sensitive since they are
_so_ sensitive (generally) to apoptosis.  and, since cd4s are 
able to induce "killing" of other cd4s (as i was reminded by d.chan)
via FAS/gld  mediated apoptosis, christopher: why are the cd 8s so 
important in tcell killing? cant the tcells w/fas,ect take care of themselves? 
    also, it seems that the pipeline idea has merit since the cells 
are dp , or at least cd4 pos, long before..why arent those levels effected?
why doesnt the differentiation machinery get out of whack and produce
large numbers of a certain cell type?  also, HIV makes a protein 
that binds up tcell transcription factors and increases transcription 
of tcell specific genes, _why doesnt_ this bias effect tcell pops?  (sorry 
that off hand i cant remember which factor, maybe tat and nfkb?) this 
should bias tcell pops and expression-since at this (thymic ) stage
in the game they are sensitive to any type of interaction/pertrubation.
    again, i buy most of your ideas, and actually hadnt thought
of why the cd8 compt hasnt been effected-i guess the dogmatic thing
and what i read can sometimes kill my free thinking-but i think my
questions are valid.  this one should get some conversation going?
    (does the nef siv story fit with your idea with tax and htlv1-
that nef mutants _dont_ cause siv becasue the cells now apoptose?)

ralph






Ralph M. Bernstein
Dept of Micro/Immuno
University of Arizona
Ph: 602 626 2585
Fx: 602 626 2100



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