Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 775K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Vivinus-Nebot, M. Articles by Bernard, A. Search for Related Content PubMed PubMed Citation Articles by Vivinus-Nebot, M. Articles by Bernard, A. Social Bookmarking                            What's this?

© The Rockefeller University Press, 0021-9525/1999//563 $5.00
The Journal of Cell Biology, Volume 144, Number 3, , 1999 563-574

Laminin 5 in the Human Thymus: Control of T Cell Proliferation via ₆β₄ Integrins

Mylène Vivinus-Nebot^*,, Michel Ticchioni^*,, Florence Mary^*, Paul Hofman, Vito Quaranta^||, Patricia Rousselle^¶, and Alain Bernard^*,

^* Institut National de la Santé et de la Recherche Médicale, U343, Nice 06202, France; Laboratoire Central d'Immunologie, Centre Hospitalier Universitaire, Nice 06202, France; Laboratoire d'Anatomie Pathologique, Centre Hospitalier Universitaire, Nice 06002, France; ^|| Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037; and ^¶ Centre National de la Recherche Scientifique, UPR 412, Lyon 69367, France

Laminin 5 (₃β₃₂) distribution in the human thymus was investigated by immunofluorescence on frozen sections with anti-₃, -β₃, and -₂ mAbs. In addition to a linear staining of subcapsular basal laminae, the three mAbs give a disperse staining in the parenchyma restricted to the medullary area on a subset of stellate epithelial cells and vessel structures. We also found that laminin 5 may influence mature human thymocyte expansion; while bulk laminin and laminin 2, when cross-linked, are comitogenic with a TCR signal, cross-linked laminin 5 has no effect. By contrast, soluble laminin 5 inhibits thymocyte proliferation induced by a TCR signal. This is accompanied by a particular pattern of inhibition of early tyrosine kinases, including Zap 70 and p59^fyn inhibition, but not overall inhibition of p56^lck. Using a mAb specific for ₆β₄ integrins, we observed that while ₃β₁ are known to be uniformly present on all thymocytes, ₆β₄ expression parallels thymocyte maturation; thus a correspondence exists between laminin 5 in the thymic medulla and ₆β₄ on mature thymocytes. Moreover, the soluble Ab against ₆β₄ inhibits thymocyte proliferation and reproduces the same pattern of tyrosine kinase phosphorylation suggesting that ₆β₄ is involved in laminin 5–induced modulation of T cell activation.

Key Words: laminin 5 • thymus • T cell • integrins • cellular activation

Abbreviations used in this paper: APY, anti-phosphotyrosine; Ab, antibody; ECM, extracellular matrix; GAR, goat anti–rabbit immunoglobulins; IP, immunoprecipitation; pAb, polyclonal antibody; PE, phycoerythrin.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Facebook

Reddit

Technorati

Twitter

This article has been cited by other articles:

• Sulka, B., Lortat-Jacob, H., Terreux, R., Letourneur, F., Rousselle, P. (2009). Tyrosine Dephosphorylation of the Syndecan-1 PDZ Binding Domain Regulates Syntenin-1 Recruitment. J. Biol. Chem. 284: 10659-10671 [Abstract] [Full Text]  
• Gorfu, G., Virtanen, I., Hukkanen, M., Lehto, V.-P., Rousselle, P., Kenne, E., Lindbom, L., Kramer, R., Tryggvason, K., Patarroyo, M. (2008). Laminin isoforms of lymph nodes and predominant role of {alpha}5-laminin(s) in adhesion and migration of blood lymphocytes. J. Leukoc. Biol. 84: 701-712 [Abstract] [Full Text]  
• Zhao, X., Wang, D., Zhao, Z., Xiao, Y., Sengupta, S., Xiao, Y., Zhang, R., Lauber, K., Wesselborg, S., Feng, L., Rose, T. M., Shen, Y., Zhang, J., Prestwich, G., Xu, Y. (2006). Caspase-3-dependent Activation of Calcium-independent Phospholipase A2 Enhances Cell Migration in Non-apoptotic Ovarian Cancer Cells. J. Biol. Chem. 281: 29357-29368 [Abstract] [Full Text]  
• Drumea-Mirancea, M., Wessels, J. T., Muller, C. A., Essl, M., Eble, J. A., Tolosa, E., Koch, M., Reinhardt, D. P., Sixt, M., Sorokin, L., Stierhof, Y.-D., Schwarz, H., Klein, G. (2006). Characterization of a conduit system containing laminin-5 in the human thymus: a potential transport system for small molecules. J. Cell Sci. 119: 1396-1405 [Abstract] [Full Text]  
• Savino, W., Mendes-da-Cruz, D. A., Smaniotto, S., Silva-Monteiro, E., Villa-Verde, D. M. S. (2004). Molecular mechanisms governing thymocyte migration: combined role of chemokines and extracellular matrix. J. Leukoc. Biol. 75: 951-961 [Abstract] [Full Text]  
• Vivinus-Nebot, M., Rousselle, P., Breittmayer, J.-P., Cenciarini, C., Berrih-Aknin, S., Spong, S., Nokelainen, P., Cottrez, F., Marinkovich, M. P., Bernard, A. (2004). Mature Human Thymocytes Migrate on Laminin-5 with Activation of Metalloproteinase-14 and Cleavage of CD44. J. Immunol. 172: 1397-1406 [Abstract] [Full Text]  
• Freywald, A., Sharfe, N., Rashotte, C., Grunberger, T., Roifman, C. M. (2003). The EphB6 Receptor Inhibits JNK Activation in T Lymphocytes and Modulates T Cell Receptor-mediated Responses. J. Biol. Chem. 278: 10150-10156 [Abstract] [Full Text]  
• Kutlesa, S., Wessels, J. T., Speiser, A., Steiert, I., Muller, C. A., Klein, G. (2002). E-cadherin-mediated interactions of thymic epithelial cells with CD103+ thymocytes lead to enhanced thymocyte cell proliferation. J. Cell Sci. 115: 4505-4515 [Abstract] [Full Text]  
• Kaldjian, E. P., Gretz, J. E., Anderson, A. O., Shi, Y., Shaw, S. (2001). Spatial and molecular organization of lymph node T cell cortex: a labyrinthine cavity bounded by an epithelium-like monolayer of fibroblastic reticular cells anchored to basement membrane-like extracellular matrix. Int Immunol 13: 1243-1253 [Abstract] [Full Text]  
• Geberhiwot, T, Assefa, D, Kortesmaa, J, Ingerpuu, S, Pedraza, C, Wondimu, Z, Charo, J, Kiessling, R, Virtanen, I, Tryggvason, K, Patarroyo, M (2001). Laminin-8 (alpha4beta1gamma1) is synthesized by lymphoid cells, promotes lymphocyte migration and costimulates T cell proliferation. J. Cell Sci. 114: 423-433 [Abstract]  
• Kim, M. G., Lee, G., Lee, S.-K., Lolkema, M., Yim, J., Hong, S. H., Schwartz, R. H. (2000). Epithelial Cell-Specific Laminin 5 Is Required for Survival of Early Thymocytes. J. Immunol. 165: 192-201 [Abstract] [Full Text]  
• Gambaletta, D., Marchetti, A., Benedetti, L., Mercurio, A. M., Sacchi, A., Falcioni, R. (2000). Cooperative Signaling between alpha 6beta 4 Integrin and ErbB-2 Receptor Is Required to Promote Phosphatidylinositol 3-Kinase-dependent Invasion. J. Biol. Chem. 275: 10604-10610 [Abstract] [Full Text]  
• Bachelder, R. E., Marchetti, A., Falcioni, R., Soddu, S., Mercurio, A. M. (1999). Activation of p53 Function in Carcinoma Cells by the alpha 6beta 4 Integrin. J. Biol. Chem. 274: 20733-20737 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents