A new study offers hope that an HIV-ravaged immune system can rebuild
itself after successful treatment with anti-HIV drugs. Researchers
supported by the National Institute of Allergy and Infectious Diseases
(NIAID) have found that the thymus gland, which produces the immune
system's T cells, appears to remain functional well into adulthood
rather than just during infancy and early childhood, as current theory
holds. They also found evidence that although HIV infection may
adversely affect the thymus, the gland continues to produce new T cells
after the infection is suppressed by intensive anti-HIV therapy. A
report of their findings is published in the Dec. 17, 1998, issue of
"This is a very promising finding because it confirms that the thymus is
active in adults and potentially can partially reconstitute an
HIV-infected individual's T cells after his or her viral load has been
driven down by highly active antiretroviral therapy (HAART)," says NIAID
Director Anthony S. Fauci, M.D. "Moreover, the technique developed to
track newly produced T cells could prove to be a valuable research tool
for monitoring immune reconstitution in HIV-infected people."
A research team led by Richard A. Koup, M.D., and Daniel C. Douek, M.D.,
Ph.D., of the University of Texas Southwestern Medical Center in Dallas,
measured a genetic byproduct of T-cell development in blood samples from
10 HIV-infected and 30 uninfected individuals. Before they are released
from the thymus, T cells generate circular fragments of DNA, dubbed
T-cell receptor rearrangement excision circles, or TRECs. Previous
studies showed that TRECS are stable and are not reproduced during
subsequent cycles of cell division. Drs. Koup, Douek and their
colleagues hypothesized that the presence of TRECS would identify T
cells that had recently left the thymus and thus serve as a marker of
Using sensitive DNA tests, the scientists showed that TRECs are present
in na´ve T cells - those that have not yet encountered their specific
antigen - but not in memory T cells - the cloned descendants of cells
that have already had such encounters.
"The fact that memory T cells lack these specific sequences," the
authors note, "suggests that TRECs are diluted during the switch from
na´ve to memory phenotype, presumably as a result of cellular
proliferation accompanying this process."
The researchers also found that TREC quantity declines significantly
with age. Still, they detected TREC-containing T cells in blood samples
from persons as old as 73 years. Elderly persons with intact thymus
glands had significantly higher TREC levels than did elderly individuals
whose thymus glands had been removed during heart surgery or other
Analysis of blood samples from a group of HIV-infected individuals
showed that their TREC levels were significantly lower than TREC levels
in blood from age-matched healthy individuals. After receiving HAART,
however, all but one of the HIV-infected individuals showed a rapid and
sustained increase in TRECs.
"Our findings suggest that thymic function is suppressed in HIV-infected
individuals and can be improved by reduction of viral load," says Dr.
Koup. "Therapies that directly improve thymic function may increase the
rate of immune reconstitution after HAART."
The study's project officer, Patricia D'Souza, Ph.D., of NIAID's
Division of AIDS, adds, "The next obvious question is to find out what
is going on in children being treated for HIV infection. The thymus is
much more active in children compared with adults. This technique
provides an exciting opportunity to monitor thymic output and immune
reconstitution in that population."
NIAID is a component of the National Institutes of Health (NIH). NIAID
conducts and supports research to prevent, diagnose and treat illnesses
such as HIV disease and other sexually transmitted diseases,
tuberculosis, malaria, asthma and allergies. NIH is an agency of the
U.S. Department of Health and Human Services.
Press releases, fact sheets and other NIAID-related materials are
available on the NIAID Web site at
HR Rodewald. The thymus in the age of retirement (editorial). Nature
396, 630-31 (1998).