AEGiS-14IAC: Enhancement of human T-lymphopoiesis by growth hormone.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Enhancement of human T-lymphopoiesis by growth hormone.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. ThOrA1484)

Napolitano LA, Chien AJ, Hanley MB, Moreno MB, Rivera J, Bare J, Stoddart CA, McCune JM
Gladstone Institute of Virology and Immunology/UCSF, San Francisco, CA, United States

BACKGROUND: Animal studies indicate that growth hormone (GH) plays an important role in mammalian thymopoiesis, raising the possibility that its administration may be of therapeutic benefit in human immunodeficiency. We previously hypothesized that GH treatment would stimulate thymopoiesis during HIV-1-infection. In a prospective study of 5 HIV-1-infected adults, we found that GH treatment was associated with a marked increase in thymic tissue in all GH recipients as measured by thymic computed tomography with quantitative density and volume analysis. Increased thymic mass was accompanied by a significant rise in circulating CD4+,CD45RA+,CD62L+ naïve T cells in all subjects, suggesting that GH enhances thymopoiesis.

RESULTS: Studies were performed to examine the mechanisms underlying GH effects on human thymopoiesis. GH was found to induce human thymic hyperplasia in a dose-dependent manner in the SCID-hu Thy/Liv mouse model. Multiparameter flow cytometry was performed to determine which thymocyte subpopulations might have expanded in response to GH. Despite a marked increase in thymic cellularity in the GH-treated animals, there was no differential expansion of any thymocyte subpopulation including rare CD34+ progenitor cells, immature CD4+CD8+ thymocytes, and mature CD4+ or CD8+ medullary thymocytes. These findings were corroborated by a series of in vitro studies. Pediatric and fetal thymic organ cultures were established in the presence of GH under a variety of conditions. No effect of GH was seen on thymocyte cell number, apoptosis, or proliferation within any thymocyte subpopulation.

CONCLUSIONS: GH treatment of HIV-1-infected adults is associated with a striking increase in thymic tissue and circulating naïve CD4+ T cells, suggesting that GH enhances human thymopoiesis. Further in vivo and in vitro analyses suggest that the primary cellular targets of GH appear to be pre-thymic hematopoietic progenitor cells or thymic stroma, and not thymocytes.

Keywords: AEGIS, Growth Hormone, Thymus Gland, T-Lymphocytes, HIV-1, HIV Infections, Hominidae, Antigens, CD4, Antigens, CD8, Antigens, CD34, Organ Culture, Flow Cytometry, Prospective Studies, Human, Animal, Adult, In Vitro, Mice, Child, immunology

020707
ThOrA1484