re cd 8 infection/ hiv not cd4 disease

Christopher Savoie savoie at
Mon Apr 3 19:16:55 EST 1995

ralph at (Ralph M Bernstein) wrote:
> ok,
> christopher,
>     i wonder, do dps in the thymus express the so called co-receptor
> "necessary"  for hiv entry? (what is it, cd 36, cd 30?)  i know that that is
> under contention now, but perhaps that could help clear up exactly when
> _any_ cell with cd4 on its surface is infected, eg, perhaps these cells
> cannot be infected intrathymically because they arent expressing that
> co-receptor?
>     and still i say that there may be a "pipeline" effect (as i said before),
> also, has anyone looked to see if dps are actually infected at all?
Here is the study (highly overlooked, even, I suppose by the authors)
that really started me on this crusade a couple of years back.  Before
this report, I had dreamed up the concept of double positive demise
of the CD8 compartment as a mechanism actually in order to explain
HTLV-I pathogenesis (HTLV integration is actually observed in the CD8
T-cells of HTLV carriers.  When I saw this paper, I realized that my 
hunch about T Cell Lukemia could be applicable to HIV.  The only problem
is that there ain't any (detectable) provirus in AIDS peripheral CD8's.

Here it is.

Unique Identifier
  Stanley SK.  McCune JM.  Kaneshima H.  Justement JS.  Sullivan M.  Boone
  E.  Baseler M.  Adelsberger J.  Bonyhadi M.  Orenstein J.  et al.
  Laboratory of Immunoregulation, National Institute of Allergy and
  Infectious Diseases, National Institutes of Health, Bethesda, Maryland
  Human immunodeficiency virus infection of the human thymus and disruption
  of the thymic microenvironment in the SCID-hu mouse.
  Journal of Experimental Medicine.  178(4):1151-63, 1993 Oct 1.
MeSH Subject Headings
  Antigens, CD4/an [Analysis]
  Antigens, CD8/an [Analysis]
  DNA, Viral/an [Analysis]
  Fluorescent Antibody Technique
  HIV/ge [Genetics]
  *HIV/ip [Isolation & Purification]
  HIV Infections/im [Immunology]
  *HIV Infections/mi [Microbiology]
  HIV Infections/pa [Pathology]
  Mice, SCID
  Microscopy, Electron
  Polymerase Chain Reaction
  RNA, Viral/an [Analysis]
  T-Lymphocyte Subsets/mi [Microbiology]
  Thymus Gland/im [Immunology]
  *Thymus Gland/mi [Microbiology]
  Thymus Gland/ul [Ultrastructure]
  Infection with the human immunodeficiency virus (HIV) results in
  immunosuppression and depletion of circulating CD4+ T cells. Since the
  thymus is the primary organ in which T cells mature it is of interest to
  examine the effects of HIV infection in this tissue. HIV infection has
  been demonstrated in the thymuses of infected individuals and thymocytes
  have been previously demonstrated to be susceptible to HIV infection both
  in vivo, using the SCID-hu mouse, and in vitro. The present study sought
  to determine which subsets of thymocytes were infected in the SCID-hu
  mouse model and to evaluate HIV-related alterations in the thymic
  microenvironment. Using two different primary HIV isolates, infection was
  found in CD4+/CD8+ double positive thymocytes as well as in both the CD4+
  and CD8+ single positive subsets of thymocytes. The kinetics of infection
  and resulting viral burden differed among the three thymocyte subsets and
  depended on which HIV isolate was used for infection. Thymic epithelial
  (TE) cells were also shown to endocytose virus and to often contain
  copious amounts of viral RNA in the cytoplasm by in situ hybridization,
  although productive infection of these cells could not be definitively
  shown. Furthermore, degenerating TE cells were observed even without
  detection of HIV in the degenerating cells. Two striking morphologic
  patterns of infection were seen, involving either predominantly thymocyte
  infection and depletion, or TE cell involvement with detectable
  cytoplasmic viral RNA and/or TE cell toxicity. Thus, a variety of cells in
  the human thymus is susceptible to HIV infection, and infection with HIV
  results in a marked disruption of the thymic microenvironment leading to
  depletion of thymocytes and degeneration of TE cells.
Registry Numbers
  0 (Antigens, CD4).  0 (Antigens, CD8).  0 (DNA, Viral).  0 (RNA, Viral).

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