VIRUSMYTH HOMEPAGE
DISPUTING THE CD4 CELL THEORY
"Evidence suggests decrease in CD4 + T cells is not a death sentence"
Jim Kling (jkling@nasw.org) interviewed Louis J. Picker, associate director
of the Vaccine and Gene Therapy Institute at the Oregon Health Sciences
University, about his "Hot Paper" published in Nature Medicine (1).
The interview was published in The Scientist on 14 May 2001.
"For several years, HIV-specific CD4+ memory/effector T cells (CD4+ T cells)
have been at the heart of a debate surrounding the progression of AIDS. ...if the
cell count were low or nonexistent, clinical AIDS was probably just around
the corner."
"That argument did not sit well with Louis J. Picker, associate director of
the Vaccine and Gene Therapy Institute at Oregon Health Sciences University
in Portland. "The proliferation studies [used to measure the presence of
CD4+ T cells] have a six-day readout time," he says. "It's been shown that
you're measuring the overall ability of T cells to proliferate under those
conditions." In other words, cells that don't thrive in vitro might die in
culture. At the experiment's end, those cells would be under-represented,
leading researchers to conclude mistakenly that little or no CD4+ T cells
were present in the sample.(2)"
""The absence of these cells was being touted as the 'missing link.' That is,
the defect responsible for why the immune system doesn't control HIV infection.
Our data suggests it is more complicated than that.""
"Picker has made a career of developing flow cytometry methods, and he
applied his work, already completed on other viral systems, to HIV. He and
his colleagues spent five years perfecting the conditions that would
provide consistent T cell activation... This way, the cells would not go through
any replication cycles and the results would not be skewed."
"As indicated in this Hot Paper, Picker and colleagues found that these patients
had surviving CD4+ T cell populations, albeit at low levels. Previous observations
had indicated otherwise."
""There was no clear-cut association between viral load and the [numbers] of
these cells," says Picker, suggesting that HIV-specific CD4+ T cell levels
are not an accurate marker of disease progression."
Read the whole
article from The Scientists.
References:
(1) C.J. Pitcher, C. Quittner, D.M. Peterson, M. Connors, R.A. Koup, V.C.
Maino, L.J. Picker, "HIV-1-specific CD4(+) T cells are detectable in most
individuals with active HIV-1 infection, but decline with prolonged viral
suppression," Nature Medicine, 5:518-525, May 1999.
(2) L.J. Picker and V.C. Maino, "The CD4+ T cell response to HIV-1," Current
Opinion in Immunology, 12:381-6, 2000.
VIRUSMYTH HOMEPAGE
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