Analysis by in Situ Hybridization of Cytokine Mrna Expression in the Murine Developing Thymus

[en] We have used in situ hybridization to investigate the expression of IL-1, IL-2, IL-4, IL-6 and IFN-gamma genes by thymic cells during fetal development in mice. Two waves of mRNAs were detected in thymic cells for IL-1 at days 16 and 19 of gestation, for IL-2 at days 14 and 18, and for IL-4 at days 14 and 16. Three peaks for IL-6 were observed at days 13, 17 and around birth. Finally, only one peak of cells positive for IFN-gamma was detected. Whereas cells positive for IL-1 were generally grouped and more often localized in the external area of the thymus, the other positive cells were isolated and evenly distributed in the thymus. Our results illustrated the presence of cytokine transcripts in the developing thymus following a developmentally controlled sequence and support the hypothesis that cytokines could play a role in T cell development.

Disciplines :

Anatomy (cytology, histology, embryology...) & physiology

Author, co-author :

Deman, J.

Humblet, Chantal ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie - Cytologie

Martin, M. T.

Boniver, Jacques ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques

Defresne, Marie-Paule ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie - Cytologie

Language :

English

Title :

Analysis by in Situ Hybridization of Cytokine Mrna Expression in the Murine Developing Thymus

Publication date :

October 1994

Journal title :

International Immunology

ISSN :

0953-8178

eISSN :

1460-2377

Publisher :

Oxford University Press, Oxford, United Kingdom

Volume :

Issue :

Pages :

1613-9

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 15 November 2010

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Bibliography

Stutman, O. 1978. Intrathymic and extrathymic T cell maturation. Immunol. Rev. 42:138.
Fowlkes, B. J. and Pardoll, D. M. 1989. Molecular and cellular events of T cell development. Adv. Immunol. 44:207.
Shortman, K. 1992. Cellular aspects of T-cell development. Curr. Opinion Immunol. 4:140.
Scollay, R. 1991. T-cell subset relationships in thymocyte development. Curr. Opinion Immunol. 3:204.
Ransom, J., Fisher, M" Mosmann, T., Yokota, T., Deluca, D" Schumacher, J. and Zlotnik, A. 1987. Interferon-yis produced by activated immature mouse thymocytes and inhibits the IL-4-induced proliferation of immature thymocytes. J. Immunol. 139:4102.
Ceredig, R. 1986. Proliferation in vitro and interleuklne production by 14-day fetal and adult CD8CD4 thymocytes. J. Immunol. 137:2260.
Man der Pouw-Kraan, T., Man Kooten, C" Rensink, I. and Aarden, L. 1992. IL-4 production by human T cells: Differential regulation of IL-4 vs. IL-2 production. Eur. J. Immunol. 22:1237.
Gutierrez, J. C. and Palacios, R. 1991. Heterogeneity of thymic epithelial cells in promoting T-lymphocyte differentiation in vitro. Proc. Natl Acad. Sci. USA 88:642.
Robert, F., Geenen, V., Schoenen, J., Burgeon, E., De Groote, D., Defresne, M. P., Legros, J. J. and Franchimont, P. 1991. Colocalization of immunoreactive oxytocin, vasopressin and interleukin-1 in human thymic epithelial neuroendocrine cells. Brain, Behav. Immun. 5:102.
Denning, S. M., Kurtzberg, J., Le, P. T., Tuck, D. T., Singer, K. H. and Haynes, B. F. 1988. Human thymic epithelial cells directly induce activation of autologous immature thymocytes. Proc. Natl Acad. Sci. USA 85:3125.
Eshel, I., Savion, N. and Shoham, J. 1990. Analysis of thymic stromal cell subpopulations grown in vitro on extracellular matrix in defined medium. II. Cytokine activities In murine thymic epithelial and mesenchymal cell culture supematants. J. Immunol. 144:1563.
Ranges, G. E., Fisher, M., Mosmann, T., Yokota, T., DeLuca, D., Schumacher, J. and Zlotnik, A. 1988. Tumor necrosis factor-a/cachectin is a growth factor for thymocytes. J. Exp. Med. 167:1472.
Suda, T., Murray, R., Fisher, M., Yokota, T. and Zlotnik, A. 1990. TNF-a and P40 induce day 15 murine fetal thymocyte proliferation In combination with IL-2. J. Immunol. 144:1783.
Defresne, M. P., Humblet, C., Rongy, A. M., Greimers, R. and Boniver, J. 1990. Effect of IFN gamma and tumor necrosis factoralpha on lymphoepithelial interactions within thymic nurse cells. Eur. J. Immunol. 20:42.
Lo, D. and Sprent, J. 1986. Exogenous control of l-A expression in fetal thymus expiants. J. Immunol. 137:1772.
Murray, R., Suda, T., Wrighton, F. and Zlotnick, A. 1989 IL-7 is a growth and maintenance factor for mature and immature thymocyte subsets. Int. Immunol. 1:526.
Watson, J. D., Morrissey, P. J., Namen, A. E., Conlon, P. J. and Widmer, M. B. 1989. Effect of IL-7 on the growth of fetal thymocytes in culture. J. Immunol. 143:1215.
Suda, T., Murray, R., Guidos, C., Zlotnik, A. 1990. Growth-promoting activity of IL-1 a, IL-6 and TNFa in combination with IL-2, IL-4 or IL-7 on murine thymocytes. J. Immunol. 144:3039.
Carding, S. R., Jenkinson, E. J., Kingston, R., Hayday, A. C., Bottomly, K. and Owen, J. J. T. 1989. Developmental control of fymphokine gene expression in fetal thymocytes during T-cell ontogeny. Proc. Natl Acad. Sci. USA 86:3342.
Deman, J., Delvenne, P., Martin, M. T" Boniver, J. and Defresne, M. P. 1992. Analysis by in situ hybrization of cells expressing mRNA for TNFa in the murine developing thymus. Dev. Immunol. 2:103.
Gray, P. W., Glaister D., Chen, E., Goeddel, D. V. and Pennica. 1986. Two interleukin 1 genes in the mouse: Cloning and expression of the cDNA for murine interleukin 1p. J. Immunol. 137:3644.
Fuse, A., Fujita, T" Yasumitsu, H., Kashima, N., Hasegawa, K. and Taniguchi, T. 1984. Organization and structure of the mouse interleukin-2 gene. Nucleic Acids Res. 12:9323.
Noma, Y., Sideras, P., Naito, T., Bergstedt-Lindquist, S., Azuma, C., Severinson, E., Tanabe, T., Kinashi, T" Matsuda, F., Yaoita, Y. and Honjo, T. 1986. Cloning of cDNA encoding the murine lgG1 induction factor by a novel strategy using SP6 promoter. Nature 319:640.
Simpson, R. J., Moritz, R. L, Wen Roost, R and Ven Snick, J. 1988. Characterization of a recombinant murine interleukin 6: Assignment of disulfide bonds. Biochem. Biophys. Res. Commun. 157:364.
Gray, P. W. and Goeddel, D. V. 1983. Cloning and expression of murine immune interferon cDNA. Proc. Natl Acad. Sci. USA 80:5842.
Fransen, L, Muller, R., Marmenout, A., Tavemier, J., Ven der Heyden, J., Kawashima, E., Chollet, A., Tizard, R., Ven Heuverswyn, H., Van Vliet, A., Ruysschaert, M. R. and Fiers, W. 1985. Molecular cloning of mouse tumor necrosis factor cDNA and its eukariotic expression. Nucleic Acids Res. 13:4417.
Maniatis, T" Fritsch, E. F. and Sambrook, J. 1982 Molecular Cloning. A Laboratory Manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
Wiles, M V., Ruiz, P. and Imhof, B. A. 1992. Interleukin-7 expression during mouse thymus development. Eur. J. Immunol 22:1037.
Dallman, M. J., Montgomery, R. A., Larsen, C. P., Winders, A. and Xells, A. F. 1991. Cytokine gene expression-analysis using northern blotting, polymerase chain reaction and in situhybridization. Immunol Rev. 119:164.
Carding, S. R., Hayday, A. C. and Bottomly, K. 1991. Cytokines in T-cell development. Immunol. Today 12:239.
Moore, N. C., Anderson, G., Smith, C. A., Owen, J. J T. and Jenkinson, E. J. 1993. Analysis of cytokine gene expression in subpopulations of freshly isolated thymocytes and thymic stromal cells using semiquantitative polymerase chain reaction. Eur. J. Immunol. 23:922.
Mandel, T. E. and Kennedy, M. M. 1978. The differentiation of murine thymocytes in vivo and in vitro. Immunology 35:317.
Vfein Ewijk, W. 1991. T-cell differentiation is influenced by thymic microenvironments. Annu. Rev. Immunol. 9:591.
Jenkinson, E. J., Kingston, R. and Owen, J. J. T. 1987. Importance of IL-2 receptors in intra-thymic generation of cells expressing T-cell receptors. Nature 329:160.
Plum, J. and De Smedt, M. 1988. Differentiation of thymocytes in fetal organ culture: Lack of evidence the functional rote of the interleukin 2 receptor expressed by thymocytes. Eur. J. Immunol. 18:795.
Plum, J., De Smedt, M., Tlson, B. and Leclercq, G. 1989. Influence of antibodies neutralizing cytokines on murine fetal thymic organ cultures. Thymus 13:83.
Plum, J., Koning, F" Leclercq, G., Tison, B. and De Smedt, M. 1990. Expansion of large granular lymphocytes in IL-2 driven 14-day-old fetal thymocytes in organ culture. J. Immunol. 144:3710.
Zanders, G. A. and Boyd, R. L. 1990. The effects of interleukin 2 on early and late thymocyte differentiation in fetal thymus organ culture. Int. Immunol. 2:4671.
Cordier, A. C. and Haumont, S. M. 1980. Development of thymus, parathyroids and ultimo-branchial bodies in NMR1 and nude mice. Am. J. Anat. 157:227.
Haynes, C., Denning, S. M., Singer, K. H. and Kurrtzberg, J. 1989. Ontogeny of T-cell precursors. Immunol. Today 10:87.
Haaijman, J. J., Micklem, S. H., Ledbetter, J. A., Dangh, J. L. and Herzenberg, L. A. 1981. T cell ontogeny. J. Exp. Med. 153:605.
Kyewski, B. A. 1986. Thymic nurse cells: Possible sites of T-cell selection. Immunol. Today 7:375.
MacConkey, D. J., Hartzell, P., Chow, S. C., Orrenius, S. and Jondal, M. 1990. IL-1 inhibits T cell receptor-mediated apoptosis in immature thymocytes. J. Biol. Chem. 265:3009.
Nieto, M. A., Gonzalez, A., Lopez-Rivas, A., Diaz-Espada, F. and Gambon, F. 1990. IL-2 protects against anti-CDS-induced cell death in human medullary thymocytes. J. Immunol. 145:1364.
Lawetzhy, A., Kubbies, M. and Honlg, T. 1991. Rat first wave’ mature thymocytes: Cycling lymphoblats that are sensitive to activation-induced cell death but rescued by interleukin 2. Eur. J. Immunol. 21:2599.
Lewis, D. B., YU, C. C., Forbush, K. A., Carpenter, J., Sato, T. A., Grossman, A., Liggit, D. H. and Perlmutter, R. M. 1991. IL-4 expressed in situ selectively alters thymocyte development. J. Exp. Med. 173:89.
Schorle, H., Hottschke, T., Hunig, T., Schimpl, A. and Horak, I. 1991. Development and function of T cells in mice rendered IL-2 deficient by gene targeting. Nature 352:621.
Kuhn, R., Rajewski, K. and Muller, W. 1991. Generation and analysis of IL-4 deficient mice. Science 25:707.
Sadlack, B., Kohn, R., Schorle, H" Rajewski, K., Muller, W. and Horak, I. 1994. Development and proliferation of lymphocytes in mice deficient for both interleukins-2 and -4. Eur. J. Immunol. 24:281.
Nakarto, N., Kikutani, H. and Kishimoto, T 1990. Differential effects of IL-2 and IL-6 on the development of three distinct precursor T-cell populations in the thymus. Dev. Immunol. 1:77.