Abstract
A thymic stromal cell line, TFGD, was established from a thymic tumor mass developed spontaneously in p53 knock out. mouse, and was found to produce cytokines that could induce bone marrow hematopoietic stem cells (HSCs) to differentiate into macrophages. The cytokines produced by the TFGD line were assessed by immunoassays. High level of macrophagecolony stimulating factor (M-CSF) and interleukin (IL)-6 was detected in the TFGD-culture supernatant, whereas granulocyte/macrophage-colony stimulating factor (GM-CSF), IL-3, IL-4, IL-5, IL-13, or interferon (IFN)-γ was undetectable. Blocking experiments showed that anti-M-CSF monoclonal antibody could neutralize the differentiation-inducing activity shown by the TFGD-culture supernatant. Dot blot analysis of the total RNA isolated from the cultured fetal thymic stromal cells showed that M-CSF transcripts were expressed in the normal thymus. These observations, together with the earlier finding, that M-CSF plus IL-6 is the optimal combination of cytokines for the induction of macrophage differentiation from HSCsin vitro, may indicate that thymic macrophages could be generated within the thymus by cytokines involving M-CSF.
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References
Amsen, D. and Kruisbeek, A. M., Thymocyte selection: not by TCR alone.Immunol. Rev., 165, 209–229 (1998).
Ardavin, C., Wu, L., Li, C.-L. and Shortman, K. Thymic dendritic cells and T cells develop simultaneously within the thymus from a common precursor population.Nature, 361, 761–763 (1993).
Fowlkes, B. J. and Schweighoffer, E., Positive selection of T cells.Curr. Opin. Immunol., 7, 188–195 (1995).
Godfrey, D., Kennedy, J., Suda, T. and Zlotnik, A., A developmental pathway involving four phenotypically and functionally distinct subsets of CD−CD4−CD8− triplenegative adult mouse thymocytes defined by CD44 and CD25 expression.J. Immunol., 150, 4244–4252 (1993).
Jansen, J. H., Kluin-Nelemans, J. C., van Damme, J., Weintjens, G. J., Willemze, R. and Fibbe, W. E., Interleukin 6 is a permissive factor for monocytic colony formation by human hematopoietic cells.J. Exp. Med., 175, 1151–1154 (1992).
Kendall, M. D., Lane, D. P. and Schumacher, U., Immunohistochemical and ultrastructural evidence of myelopoiesis in the scid/scid mouse thymus.Histochem. J., 311, 651–660 (1999).
Kisielow, P. and von Boehmer, H., Development and selection of T cells: Facts and puzzles.Adv. Immunol. 58, 87–209 (1991).
Lee, C-K., Kim, K., Geiman, T. M., Murphy, W. J., Muegge, K. and Durum, S. K., Cloning thymic precursor cells: Demonstration that individual pro-T1 cells have dual T-NK potential and individual pro-T2 cells have dual αβ-γσ T cell potential.Cell. Immunol., 191, 139–144 (1998).
Marquez, C., Trigueros, C., Franco, J. M., Ramiro, A. R., Carrasco, Y. R., Lopez-Botet, M. and Toribio, M. L., Identification of a common developmental pathway for thymic natural killer cells and dendritic cells.Blood, 91, 2760–2771 (1998).
Metcalf, D., The molecular biology and functions of the granulocyte-macrophage colony stimulating factors.Blood, 67, 257–267 (1986).
Peault, B., Khazaal, I. and Weissman, I. L., In vitro development of B cells and macrophages from early mouse fetal thymocytes.Eur. J. Immunol., 24, 781–784 (1994).
Saunders, D., Lucas, K., Ismaili, J., Wu, L., Maraskovsky, E., Dunn, A. and Shortman, K., Dendritic cell development in the culture from thymic precursor cells in the absence of granulocyte/macrophage colony-stimulating factor.J. Exp. Med., 184, 2185–2196 (1996).
Scollay, R., Smith, J., and Stauffer, V., Dynamics of early T cells: prothymocyte migration and proliferation in the adult mouse thymus.Immunol. Rev., 91, 129–157 (1986).
Shortman, k., Vremec, D., Corcoran, L. M., Georgopoulos, K., Lucas, K. and Wu, L., The linkage between T-cell and dendritic cell development in the mouse thymus.Immunol. Rev., 165, 39–46.
Surh, C. D. and Sprent, J., T-cell apoptosis detected in situ during positive and negative selection in the thymus.Nature, 372, 100–103 (1994).
Tushinski, R. J., Oliver, I. T., Guilbert, L. J., Tynan, P. W., Warner, J. R. and Stanley, E. R., Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy.Cell, 28, 71–81 (1982).
Vicente, A., Varas, A., Moreno, J., Sacedon, R., Jimenez, E., and Zapata, A. G., Ontogeny of rat thymic macrophages: Phenotypic characterization and possible relationships between different cell subsets.Immunology, 85, 99–105 (1995).
Wong, G. G., Temple, P. A., Leary, A. C., Witek-Giannotti, J. S., Yang, C. Y., Ciarletta, A. B., Chung, M., Murtha, P., Kriz, R., Kaufman, R. J., Ferenz, C. R., Sibley, B. S., Tunrner, K. J., Hewick, R. M., Clark, S. C., Yanai, N., Yamada, M., Saito, M., Motoyoshi, K. and Takaku, F., Human CSF-1: Molecular cloning and expression of 4-kb cDNA encoding the human urinary protein.Science, 235, 1504–1508 (1987).
Wu, L., Antica, M., Johnson, G. R., Scollay, R. and Shortman, K., Developmental potential of the earliest precursor cells from the adult thymus.J. Exp. Med., 174, 1617–1627 (1991).
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Lee, CK., Kim, J.K., Kim, K. et al. A mouse thymic stromal cell line producing macrophage-colony stimulating factor and interleukin-6. Arch Pharm Res 23, 252–256 (2000). https://doi.org/10.1007/BF02976455
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DOI: https://doi.org/10.1007/BF02976455