title: Young, proliferative thymic epithelial cells engraft and function in aging thymuses.
abstract: The thymus reaches its maximum size early in life and then begins to shrink, producing fewer T cells with increasing age. This thymic decline is thought to contribute to age-related T cell lymphopenias and hinder T cell recovery after bone marrow transplantation. Although several cellular and molecular processes have been implicated in age-related thymic involution, their relative contributions are not known. Using heterochronic parabiosis, we observe that young circulating factors are not sufficient to drive regeneration of the aged thymus. In contrast, we find that resupplying young, engraftable thymic epithelial cells (TECs) to a middle-aged or defective thymus leads to thymic growth and increased T cell production. Intrathymic transplantation and in vitro colony-forming assays reveal that the engraftment and proliferative capacities of TECs diminish early in life, whereas the receptivity of the thymus to TEC engraftment remains relatively constant with age. These results support a model in which thymic growth and subsequent involution are driven by cell-intrinsic changes in the proliferative capacity of TECs, and further show that young TECs can engraft and directly drive the growth of involuted thymuses.
authors: Joslin Diabetes Center, Boston, MA 02215; Harvard Stem Cell Institute, Cambridge, MA 02138;
authors: Mi-Jeong
authors: MJ
authors: Kim
authors: Joslin Diabetes Center, Boston, MA 02215; Harvard Stem Cell Institute, Cambridge, MA 02138; Howard Hughes Medical Institute, Cambridge, MA 02138; and Department of Stem Cell and Regenerative Biology, Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Harvard University, Cambridge, MA 02138.
authors: Christine M
authors: CM
authors: Miller
authors: Joslin Diabetes Center, Boston, MA 02215; Harvard Stem Cell Institute, Cambridge, MA 02138; Howard Hughes Medical Institute, Cambridge, MA 02138; and Department of Stem Cell and Regenerative Biology, Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Harvard University, Cambridge, MA 02138.
authors: Jennifer L
authors: JL
authors: Shadrach
authors: Joslin Diabetes Center, Boston, MA 02215; Harvard Stem Cell Institute, Cambridge, MA 02138; Howard Hughes Medical Institute, Cambridge, MA 02138; and Department of Stem Cell and Regenerative Biology, Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Harvard University, Cambridge, MA 02138.
authors: Amy J
authors: AJ
authors: Wagers
authors: Joslin Diabetes Center, Boston, MA 02215; Harvard Stem Cell Institute, Cambridge, MA 02138; thomas.serwold@joslin.harvard.edu.
authors: Thomas
authors: T
authors: Serwold
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000637:transplantation*; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010227:Parabiosis; D013950:Thymus Gland / Q000254:growth & development*