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Growth Hormone Modulates Thymocyte Development in Vivo through a Combined Action of Laminin and CXC Chemokine Ligand 12

Institut National de la Santé et de la Recherche Médicale/Fiocruz Associate Laboratory of Immunology, Laboratory on Thymus Research (S.S., D.M.S.V.-V., W.S.), Department of Immunology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21045-900, Brazil; Department of Morphology, Federal University of Alagoas (S.S.), Maceió 57072-970, Brazil; Hôpital Necker, Unité Mixte de Recherche 8147 (S.S., J.-M.P., M.D., W.S.), and Institut National de la Santé et de la Recherche Médicale, Unité 344 (M.-C.P.-V., W.S.), 75743 Paris Cedex 15, France; and National Institute of Aging, National Institutes of Health (V.d.M.-C.), Baltimore, Maryland 21224

Address all correspondence and requests for reprints to: Dr. Wilson Savino, Laboratory on Thymus Research, Department of Immunology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Avenue Brasil 4365, Manguinhos, 21045-900 Rio de Janeiro, Brazil. E-mail: savino{at}fiocruz.br.

Previous evidence indicates that GH modulates thymic cell migration. In this study we approached this issue in vivo, studying thymocyte migration in GH transgenic animals and in normal mice treated intrathymically with GH. Extracellular matrix and chemokines are involved in thymocyte migration. In this respect, thymocyte adhesion to laminin was higher in GH-treated animals than controls, and the numbers of migrating cells in laminin-coated Transwells was higher in GH-transgenic and GH-injected mice. Additionally, CXC chemokine ligand 12 (CXCL12)-driven migration was higher in GH-Tg and GH-treated animals compared with controls. Interestingly, although CXCR4 expression on thymocytes did not change in GH-Tg mice, the CXCL12 intrathymic contents were higher. We found that CXCL12, in conjunction with laminin, would additionally enhance the migration of thymocytes previously exposed to high concentrations of GH in vivo. Lastly, there was an augmentation of recent thymic emigrants in lymph nodes from GH-Tg and GH-injected animals. In conclusion, enhanced thymocyte migration in GH transgenic mice as well as GH-injected mice results at least partially from a combined action of laminin and CXCL12. Considering that GH is presently being used as an adjuvant therapeutic agent in immunodeficiencies, including AIDS, the concepts defined herein provide important background knowledge for future GH-based immune interventions.

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