Scientists at the Gladstone Institute of Virology and Immunology (GIVI) and the University of California, San Francisco (UCSF) have found that therapy can be used to stimulate the production of “T” cells in adults with HIV infection.
HIV disease destroys T-cells, leading to collapse of the immune system and severe infection. The thymus gland, which produces T-cells, gradually loses function over time and becomes mostly inactive during adulthood. Because the thymus gland does not function well in adults, it is difficult for HIV-infected adults to make new T-cells. Therapies that stimulate the thymus to produce new T-cells could help HIV-infected patients to rebuild their embattled immune systems.
Although it has been long assumed that the thymus cannot be reactivated in humans, research published in the March issue of the Journal of Clinical Investigation, shows that the thymus can be stimulated to produce more T-cells. This study is the first to show that pharmacologic therapies can be used to enhance human thymic function.
Based on promising animal studies suggesting that growth hormone (GH) enhances thymic function in aged mice, Gladstone and UCSF investigators conducted a prospective randomized research study that yielded an exciting observation: GH increased thymic mass and T-cells in humans. The investigators studied 22 HIV-infected adults for 2 years. One half of study participants were randomly assigned to continue their usual HIV therapy and to receive GH in the first year (“GH Arm”), and the other half continued their usual HIV therapy without GH treatment (“Control Arm”).
In the second year of the study, Control Arm participants received GH, and GH Arm participants were studied off GH. Immune analyses were performed regularly in all study participants. The thymus was assessed by computed tomography (CT) scans, and the numbers and types of immune cells in the blood were determined by an advanced method called multiparameter flow cytometry.
All study participants had been receiving effective HIV therapy for at least one year (average duration of HIV therapy was approximately 3 years) with good suppression of the virus. Despite effective therapy, they still had an unusually low number of “CD4” T-cells, a type of T cell that is essential for normal immune function. At the start of the study, the patients in the two arms did not differ in average duration of effective HIV therapy, amount of HIV in the blood, age, thymic mass or in a large number of important immunologic measurements.
The results were very encouraging.The researchers found that GH treatment markedly increased thymic mass and appeared to double the number of newly made T-cells. On average, GH receipt was associated with a 30% increase in CD4 T-cells (2.4 fold higher than no GH). These gains continued to increase at least 3 months beyond GH discontinuation and appeared to persist for at least one year after GH discontinuation.
Release date: February 21, 2008
Source: Gladstone Institutes
Filed Under: Drug Discovery