FORSDYKE at QUCDN.QueensU.CA wrote:
: A short paper which I found useful, since I had no knowledge of IL-12.
: My 2 cents worth:
: (i) Not clear whether the effects reported are HIV specific, virus-
: infected cell-specific, or disease-specific. Would have been nice
: to have seen some controls with other disease groups.
: (ii) How do you add IL-12 "in vitro" to HIV-infected individuals? Surely a
: cruel and inhumane punishment to place someone in a bottle before giving him/
: her IL-12?:-)
: Sincerely, Don Forsdyke
: Discussion Leader. Bionet.immunology
What is interesting to me is that, there seems to be a differential
manipulation of of gene expression.It seems that the incubation of
HIV-infected PBMC's with S.aureus produced 10X less IL-12 heavy chain (p
40) and 5X less biologically active P70. This (in theory of course)
suggests that It might be HIV specific. In order to get differential
inhibition , you'd probably need a specific induction of proteins. There
are two possibilities.1) The viral proteins might exert this regulation.
2) HiV-infection causes expression of Host proteins involved in the regulation
of IL-12 synthesis.
Some people ( can't remember who) say that CD4+ cells become dysfucntional
just by having Viral genome in the Cytoplasm and not inserted into the
nucleus. If this is
true then I am gonna commit suicide. I am not disagreeing with them, but
I don't know how I could explain the mode of immunodeficiency.
One that I would like to accept, is the 2nd hypothesis that there are
Host-mediated protein expressions forced upon by HIV itself.
What I don't like, which was briefly mentioned in the paper, is that this
IL-12 deficiency doesn't seem to occur in Lymphoid tissues from the
patients. Only in their PBMC. Isn't there enough IL-12 produced by other types
of cells to allow for Th1 differentiation? This would be enough for CMI to
do its thing.
P.S.I do people inVitro-ing all the time. They don't mind. It's kind of tight
though. :)
--
Shahram Mori
Program in Molecular Biology
Dept. of chemistry and Biochemistry Box 3C
NMSU Las Cruces NM
