Abstract
Epithelial cells in the thymic medulla are conspicuous in normal adult mice, but sparse in the early fetal thymus and the thymus of adult T cell-deficient SCID mice. To examine whether growth of medullary epithelial cells (MEC) depends upon local contact with mature T cells, we used the finding that the SCID thymus is unusually permeable to mature T cells entering from the bloodstream. When SCID mice received multiple injections of mature lymph node T cells from birth, the thymus accumulated large numbers of mature TCR+ T cells of resting phenotype, but contained virtually no immature (CD4+8+) cells. The injected T cells localized in the medullary region of the thymus and led to marked regeneration of MEC. These and other data suggest that the growth of MEC is under the control of mature T cells. Placing MEC under T cell control might be a device for regulating the size and integrity of the medulla, especially during the phase of rapid thymic growth. Maintaining the cellular components of the medulla in proper balance could be critical for ensuring efficient self tolerance induction.
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Selected References
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- Adkins B., Gandour D., Strober S., Weissman I. Total lymphoid irradiation leads to transient depletion of the mouse thymic medulla and persistent abnormalities among medullary stromal cells. J Immunol. 1988 May 15;140(10):3373–3379. [PubMed] [Google Scholar]
- Adkins B., Tidmarsh G. F., Weissman I. L. Normal thymic cortical epithelial cells developmentally regulate the expression of a B-lineage transformation-associated antigen. Immunogenetics. 1988;27(3):180–186. doi: 10.1007/BF00346584. [DOI] [PubMed] [Google Scholar]
- Agus D. B., Surh C. D., Sprent J. Reentry of T cells to the adult thymus is restricted to activated T cells. J Exp Med. 1991 May 1;173(5):1039–1046. doi: 10.1084/jem.173.5.1039. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Farr A. G., Anderson S. K. Epithelial heterogeneity in the murine thymus: fucose-specific lectins bind medullary epithelial cells. J Immunol. 1985 May;134(5):2971–2977. [PubMed] [Google Scholar]
- Frey J. R., Ernst B., Surh C. D., Sprent J. Thymus-grafted SCID mice show transient thymopoiesis and limited depletion of V beta 11+ T cells. J Exp Med. 1992 Apr 1;175(4):1067–1071. doi: 10.1084/jem.175.4.1067. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jenkins M. K., Schwartz R. H., Pardoll D. M. Effects of cyclosporine A on T cell development and clonal deletion. Science. 1988 Sep 23;241(4873):1655–1658. doi: 10.1126/science.241.4873.1655. [DOI] [PubMed] [Google Scholar]
- Kanariou M., Huby R., Ladyman H., Colic M., Sivolapenko G., Lampert I., Ritter M. Immunosuppression with cyclosporin A alters the thymic microenvironment. Clin Exp Immunol. 1989 Nov;78(2):263–270. [PMC free article] [PubMed] [Google Scholar]
- Karlsson L., Surh C. D., Sprent J., Peterson P. A. A novel class II MHC molecule with unusual tissue distribution. Nature. 1991 Jun 6;351(6326):485–488. doi: 10.1038/351485a0. [DOI] [PubMed] [Google Scholar]
- Shores E. W., Van Ewijk W., Singer A. Disorganization and restoration of thymic medullary epithelial cells in T cell receptor-negative scid mice: evidence that receptor-bearing lymphocytes influence maturation of the thymic microenvironment. Eur J Immunol. 1991 Jul;21(7):1657–1661. doi: 10.1002/eji.1830210711. [DOI] [PubMed] [Google Scholar]
- Sprent J., Schaefer M., Hurd M., Surh C. D., Ron Y. Mature murine B and T cells transferred to SCID mice can survive indefinitely and many maintain a virgin phenotype. J Exp Med. 1991 Sep 1;174(3):717–728. doi: 10.1084/jem.174.3.717. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Trowbridge I. S., Lesley J., Schulte R., Hyman R., Trotter J. Biochemical characterization and cellular distribution of a polymorphic, murine cell-surface glycoprotein expressed on lymphoid tissues. Immunogenetics. 1982 Mar;15(3):299–312. doi: 10.1007/BF00364338. [DOI] [PubMed] [Google Scholar]
- Van Vliet E., Jenkinson E. J., Kingston R., Owen J. J., Van Ewijk W. Stromal cell types in the developing thymus of the normal and nude mouse embryo. Eur J Immunol. 1985 Jul;15(7):675–681. doi: 10.1002/eji.1830150707. [DOI] [PubMed] [Google Scholar]