Received May 15, 2007
Revised June 14, 2007
Accepted after revision July 3, 2007
Neuroendocrinology/Endocrinology [270]
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NEUROENDOCRINE CONTROL OF T CELL DEVELOPMENT:
ROLE OF GROWTH HORMONE IN MODULATING THYMOCYTE MIGRATION
Wilson Savino 1*
1 Oswaldo Cruz Foundation
* To whom correspondence should be addressed. E-mail: savino{at}fiocruz.br.
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Abstract |
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The thymus gland is a primary lymphoid organ, in which bone marrow-derived T cell precursors undergo differentiation, eventually leading to migration of positively selected cells to the peripheral lymphoid organs. This differentiation occurs along with cell migration in the context of the thymic microenvironment, a three-dimensional network formed by epithelial cells, macrophages, dendritic cells, fibroblasts and extracellular matrix components. A series of data clearly shows that growth hormone (GH) pleiotropically modulates thymic functions. For example, GH upregulates proliferation of thymocytes and thymic epithelial cells. Accordingly, GH-transgenic mice, as well as animals and humans treated with exogenous GH exhibit an enhanced cellularity in the organ. Additionally, this hormone stimulates the secretion of thymic hormones, cytokines and chemokines by the thymic microenvironment, as well as the production of extracellular matrix proteins, leading to increase in thymocyte migratory responses, intrathymic traffic of developing T cells, as well as the in vivo export of thymocytes from the organ, as ascertained by studies with intrathymic injection of GH in normal mice, and with GH-transgenic mice. Moreover, since GH is produced by thymocytes and thymic epithelial cells, which express GH receptors, we should consider that, in addition to the classic endocrine pathway, the GH control upon the thymus may comprise an autocrine/paracrine pathway. Finally, since GH promotes a replenishment of the thymus and increase thymocyte export, it could be envisioned as a potential adjuvant therapeutic agent in the treatment of immunodeficiencies that course with thymic atrophy.
Key Words:
Chemoreceptor, Extracellular matrix, Growth hormone
