Discovery of a marker that allows tracking of
thymus function also shows how the adult immune system might repair
itself after being damaged by the human immunodeficiency virus (HIV),
UT Southwestern Medical Center at Dallas scientists report in Nature.
The research shows that the thymus makes new T-cells throughout
adulthood and that HIV may block their production, said Richard Koup,
MD, chief of infectious diseases. The study, a collaboration
including Koup; Daniel Douek, MD, a postdoctoral fellow in infectious
diseases; and Louis Picker, MD, associate professor of pathology,
also has important implications for people whose immune system has
been damaged by cancer treatment.
For many years it was believed that the thymus only produced T-cells
in people until about age 30 years, by which time it had slowly
disappeared, replaced by fat. However, the investigators found that
patients in their 30s whose HIV infection was treated with highly
active antiretroviral therapy (HAART) produced new T-cells.
This is important because HIV patients, who have lower than normal
numbers of T-cells, are highly vulnerable to other infections, as are
cancer patients whose treatment has destroyed many of their T-cells.
T-cells can be increased by expanding the few old ones
remaining after HIV infection or cancer treatment, or through
production of new T-cells, said Koup, who holds the Jay P.
Sanford Professorship in Infectious Diseases. If you expand the
few surviving T-cells, you may not recover broad immunity to all
infections. If T-cells programmed to fight certain infections have
been destroyed, they can only be replaced by new T-cells produced by
Using a marker for TCR-rearrangement excision circles, which are
pieces of DNA produced during normal T-cell development in the
thymus, the scientists were able to estimate the number of new
T-cells produced by the thymus. The number of these cells in the
blood indicates the level at which the thymus is functioning. The
research showed that as HAART reduced the level of HIV, the number of
new T-cells increased.
The data suggest that HIV specifically inhibits the thymus
either by infecting the cells within the organ, or by affecting the
ability of the thymus to produce T-cells by an unknown
mechanism, Koup said. The investigators now will look for ways
to stimulate the thymus, thereby speeding recovery of the immune
system after HAART or cancer treatment. Now that we have a way
to measure thymus output, we will be able to test therapies that will
increase T-cell production, Koup continued.
The other researchers involved in the study are: Philip Keiser, MD,
assistant professor of internal medicine; Richard McFarland, MD,
pathology technical staff associate; Earl Gage, UT Southwestern
medical student; and researchers from Duke University Medical Center,
the National Institute of Allergy and Infectious Diseases, the
University of Minnesota Medical School, Emory University School of
Medicine, the University of Massachusetts Medical Center, and the
UCLA School of Medicine and UCLA Institute. The National Institutes
of Health and the Elizabeth Glaser Pediatric AIDS Foundation helped
fund the work.