|HIV Therapy Greatly Extends Life
of Key T Cells, Scientists Find
Interleukin-2 (IL-2), an immune-boosting drug used
experimentally in HIV therapy, greatly increases the
lifespan of certain subsets of immune system T cells
in some HIV-positive people who respond to this therapy,
discovered researchers from the National Institutes
of Health (NIH) Clinical Center and the National Institute
of Allergy and Infectious Diseases (NIAID), part of
the NIH. A report describing the study, led by the Clinical
Center’s Joseph A. Kovacs, M.D., appears online today
in The Journal of Clinical Investigation.
A hallmark of HIV infection is the progressive loss
of CD4+ T cells (a key type of white blood
cell) and the subsequent decline in the infected person’s
ability to fend off disease. NIH clinical investigators
pioneered the experimental use of IL-2 in HIV therapy
to help boost the immune systems of people with HIV
infection. Produced naturally by T cells, IL-2 is a
powerful immune system regulator. While its use in HIV
therapy is experimental and can be associated with various
side effects, IL-2 is licensed to treat certain cancers.
NIH researchers have long observed that in responsive
patients, intermittent cycles of IL-2 therapy lead to
substantial increases in the number of circulating CD4+ cells.
The mechanisms driving this increase as well as its
potential clinical significance, however, have remained
unclear, note the scientists.
Using two relatively new techniques for labeling cells,
the team demonstrated that IL-2 therapy can lead to
greatly increased numbers of new CD4+ cells. “More
remarkable than the proliferation of these cells was
how long they lived,” says Dr. Kovacs. The average lifespan
of CD4+ cells in healthy individuals as measured
with this technique is about four weeks, according to
Dr. Kovacs. In contrast, the average lifespan of CD4+ cells
in 15 HIV-positive volunteers who had received three
or more courses of IL-2 was 37.6 weeks, about nine times
In the first set of experiments, investigators infused
32 volunteers with a sugar solution containing a harmless
chemical label, deuterium (a non-radioactive, stable
isotope), for five days. Nine volunteers were HIV-positive
but had never received IL-2; 15 volunteers were HIV-positive
and had received between three and 28 courses of IL-2;
and eight volunteers were HIV-negative.
Deuterium is incorporated into the DNA of actively
dividing cells. By taking blood samples in weeks and
months following the deuterium infusion and measuring
the amount of deuterium remaining in the CD4+ T
cell DNA at each time point, the researchers could count
how many new cells were made and how long they lived.
The scientists found a marked increase in the numbers
of newly made CD4+ cells in all the HIV-positive,
IL-2 responsive volunteers. In two HIV-positive volunteers — each
of whom had received multiple five-day courses of IL-2
over several years — the researchers detected
CD4+ cells that lived for about three years,
a result Dr. Kovacs calls “quite surprising.”
Using another labeling technique, the researchers determined
that IL-2 boosts the numbers of two subsets of CD4+ cells:
naïve cells, those that have never encountered an infectious
agent; and central memory cells, those that have encountered
an infectious agent before and are primed to respond
quickly if they encounter the same agent again.
The new data complement clinical observations suggesting
that IL-2’s effects on HIV disease progression may become
apparent only in long-term follow-up, says Dr. Kovacs.
Two large, long-term efficacy trials currently underway
should provide a clearer picture of the clinical impact
of IL-2 on the course of HIV disease and its potential
role in the management of HIV-infected patients, he
adds. Information on these and other HIV clinical trials
is available at www.aidsinfo.nih.gov.
Other authors on the paper include researchers from
the NIH’s National Cancer Institute and the Science
Applications International Corporation of Frederick,
The Clinical Center is the clinical research hospital
for the NIH. Through clinical research, physicians
and scientists translate laboratory discoveries into
better treatments, therapies and interventions to
improve the nation's health.
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primary Federal agency for conducting and supporting basic,
clinical, and translational medical research, and investigates
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