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

This Article Full Text Full Text (PDF, 2023K) PPT slides of all figures Supplemental Material Index 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 JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kawakami, N. Articles by Flügel, A. Search for Related Content PubMed PubMed Citation Articles by Kawakami, N. Articles by Flügel, A. Related Collections Related Article Social Bookmarking                      What's this?

¹ Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, 82152 Martinsried, Germany
² Department of Cellular and Systems Neurobiology, Max-Planck-Institute of Neurobiology, 82152 Martinsried, Germany

CORRESPONDENCE Alexander Flügel: fluegel{at}neuro.mpg.de

We tracked pathogenic myelin basic protein-specific CD4⁺ effector T cells in early central nervous system (CNS) lesions of experimental autoimmune encephalomyelitis (EAE) by combining two-photon imaging and fluorescence video microscopy. We made two key observations: (a) the majority of the cells (65%) moved fast (maximal speed 25 µm/min) and apparently nondirected through the compact tissue; and (b) a second group of effector T cells (35%) appeared tethered to a fixed point. Polarization of T cell receptor and adhesion molecules (lymphocyte function-associated antigen 1) towards this fixed point suggests the formation of immune synapses. Nonpathogenic, ovalbumin-specific T cells were not tethered in the CNS and did not form synapse-like contacts, but moved through the tissue. After intrathecal injection of antigen, 40% of ovalbumin-specific T cells became tethered. Conversely, injection of anti–major histocompatibility complex class II antibodies profoundly reduced the number of stationary pathogenic T cells within the CNS (to 15%). We propose that rapid penetration of the CNS parenchyma by numerous autoimmune effector T cells along with multiple autoantigen-presentation events are responsible for the fulminate development of clinical EAE.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related Article

Brain-tethered T cells

Heather L. Van Epps
J. Exp. Med. 2005 201: 1691. [Full Text] [PDF]

This article has been cited by other articles:

• Copland, D. A., Wertheim, M. S., Armitage, W. J., Nicholson, L. B., Raveney, B. J. E., Dick, A. D. (2008). The Clinical Time-Course of Experimental Autoimmune Uveoretinitis Using Topical Endoscopic Fundal Imaging with Histologic and Cellular Infiltrate Correlation. IOVS 49: 5458-5465 [Abstract] [Full Text]  
• Doi, Y., Oki, S., Ozawa, T., Hohjoh, H., Miyake, S., Yamamura, T. (2008). Orphan nuclear receptor NR4A2 expressed in T cells from multiple sclerosis mediates production of inflammatory cytokines. Proc. Natl. Acad. Sci. USA 105: 8381-8386 [Abstract] [Full Text]  
• Odoardi, F., Kawakami, N., Klinkert, W. E. F., Wekerle, H., Flugel, A. (2007). Blood-borne soluble protein antigen intensifies T cell activation in autoimmune CNS lesions and exacerbates clinical disease. Proc. Natl. Acad. Sci. USA 104: 18625-18630 [Abstract] [Full Text]  
• Boissonnas, A., Fetler, L., Zeelenberg, I. S., Hugues, S., Amigorena, S. (2007). In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor. JEM 204: 345-356 [Abstract] [Full Text]  
• Odoardi, F., Kawakami, N., Li, Z., Cordiglieri, C., Streyl, K., Nosov, M., Klinkert, W. E. F., Ellwart, J. W., Bauer, J., Lassmann, H., Wekerle, H., Flugel, A. (2007). Instant effect of soluble antigen on effector T cells in peripheral immune organs during immunotherapy of autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA 104: 920-925 [Abstract] [Full Text]  
• Minguela, A., Pastor, S., Mi, W., Richardson, J. A., Ward, E. S. (2007). Feedback Regulation of Murine Autoimmunity via Dominant Anti-Inflammatory Effects of Interferon {gamma}. J. Immunol. 178: 134-144 [Abstract] [Full Text]  
• Mrass, P., Takano, H., Ng, L. G., Daxini, S., Lasaro, M. O., Iparraguirre, A., Cavanagh, L. L., von Andrian, U. H., Ertl, H. C.J., Haydon, P. G., Weninger, W. (2006). Random migration precedes stable target cell interactions of tumor-infiltrating T cells. JEM 203: 2749-2761 [Abstract] [Full Text]  
• Pastor, S., Vaccaro, C. G., Minguela, A., Ober, R. J., Ward, E. S. (2006). Analyses of TCR clustering at the T cell-antigen-presenting cell interface and its impact on the activation of naive CD4+ T cells. Int Immunol 18: 1615-1625 [Abstract] [Full Text]  
• Barcia, C., Thomas, C. E., Curtin, J. F., King, G. D., Wawrowsky, K., Candolfi, M., Xiong, W.-D., Liu, C., Kroeger, K., Boyer, O., Kupiec-Weglinski, J., Klatzmann, D., Castro, M. G., Lowenstein, P. R. (2006). In vivo mature immunological synapses forming SMACs mediate clearance of virally infected astrocytes from the brain. JEM 203: 2095-2107 [Abstract] [Full Text]  
• Gold, R., Linington, C., Lassmann, H. (2006). Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain 129: 1953-1971 [Abstract] [Full Text]  
• Agrawal, S., Anderson, P., Durbeej, M., van Rooijen, N., Ivars, F., Opdenakker, G., Sorokin, L. M. (2006). Dystroglycan is selectively cleaved at the parenchymal basement membrane at sites of leukocyte extravasation in experimental autoimmune encephalomyelitis. JEM 203: 1007-1019 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS