Growth Hormone Is a Modulator of Lymphocyte Migration

Abstract

Cell migration is crucial for intrathymic T cell differentiation and export of mature T lymphocytes to the peripheral lymphoid organs. The intrinsic regulation of T cell migration, mediated by adhesion molecules and chemokines, can be influenced by a number of endogenous factors, such as hormones, as for instance growth hormone (GH). Laminin deposition was enhanced in GH-treated mice and in GH-transgenic animals, compared with corresponding controls, and thymocyte adhesion to laminin was increased by in vivoGH treatment. An enhancing effect was also observed ex vivo in relation to the number of migrating cells in laminin-coated transwell chambers. Additionally, we found that the chemokine CXCL12, in conjunction with laminin, further enhanced the migration of thymocytes previously exposed to high concentrations of GH in vivo. Moreover, an increase in CXCL12 production has been detected in the thymus of GH-transgenic mice as well as in primary thymic epithelial cell cultures derived from these animals, as compared to age-matched wild-type counterparts. In keeping with these data, in vivo experiments showed that GH favors the trafficking of naive CD4+CD8– recent thymic emigrants to the peripheral lymph nodes. In addition, we found that migration of lymphocytes from mesenteric lymph nodes of GH-transgenic mice, triggered by the chemokine CXCL12, in conjunction with laminin or fibronectin, was enhanced, when compared to lymphocytes from control mice. Since GH-based therapy has been used in human and experimental infectious diseases, this hormone can be envisioned as an additional therapeutic tool in situations in which increasing lymphocyte numbers and migration are required for correcting a given pathological state.