Submitted April 8, 2008
Accepted June 20, 2008
Exogenous insulin-like growth factor 1 enhances thymopoiesis predominantly through thymic epithelial cell expansion
Yu-Waye Chu*, Sabrina Schmitz, Baishakhi Choudhury, William Telford, Veena Kapoor, Susan Garfield, David Howe, and Ronald E Gress
Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD, United States
Laboratory of Experimental Carcinogenesis, National Institutes of Health, Bethesda, MD, United States
* Corresponding author; email: chuy{at}mail.nih.gov.
Insulin-like growth factor 1 (IGF-1) enhances thymopoiesis but given the broad distribution of IGF-1 receptors (IGF-1R), its mechanism of action has remained unclear. To identify points of thymic regulation by IGF-1, we examined its effects on T-cell precursors, thymocytes and thymic epithelial cells (TEC) in normal and genetically altered mice. In thymus-intact but not thymectomized mice, IGF-1 administration increased peripheral naive and recent thymic emigrant (RTE) populations, demonstrating its effect on T-cell production, not peripheral expansion. IGF-1 administration increased bone marrow LSK (Lineage-, Sca-1+, c-kit+) precursor proliferation and peripheral LSK populations, increased thymocyte populations in a sequential wave of expansion, and proportionately expanded TEC subpopulations and enhanced their chemokine expression. To separate IGF-1 effects on thymocytes and TEC, we generated mice lacking IGF-1R on thymocytes and T-cells. Thymocyte and RTE numbers were decreased in these mice, but IGF-1 treatment produced comparable thymocyte numbers as similarly treated wild-type mice. We additionally separated thymic from LSK specific effects by demonstrating that IGF-1 increased thymocyte numbers despite impaired ETP importation in PSGL-1KO mice. These results indicate the critical point thymic function regulation by IGF-1 involves TEC expansion regulating thymocyte precursor entry and facilitating thymocyte development.
