This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Medana, I. Articles by Neumann, H. Search for Related Content PubMed PubMed Citation Articles by Medana, I. Articles by Neumann, H.

(American Journal of Pathology. 2001;159:809-815.)
© 2001 American Society for Investigative Pathology

Short Communications

Transection of Major Histocompatibility Complex Class I-Induced Neurites by Cytotoxic T Lymphocytes

Isabelle Medana^*, Marianne A. Martinic, Hartmut Wekerle^* and Harald Neumann^*

From the Department of Neuroimmunology,^*
Max-Planck-Institute of Neurobiology, Martinsried, Germany; and the Department of Pathology,
Experimental Immunology, University of Zurich, Zurich, Switzerland

Damage to neurites with transection of axons and spheroid formation is commonly noted in the central nervous system during viral and autoimmune diseases such as multiple sclerosis, but it remains open whether such changes are caused primarily by immune mechanisms or whether they are secondary to inflammation. The present experiments explored whether neurites can be directly attacked by cytotoxic T lymphocytes (CTLs). Cultured murine neurons induced by interferon- and tetrodotoxin to express major histocompatibility complex class I were pulsed with a dominant peptide of the lymphochoriomeningitis virus envelope glycoprotein (GP33) and then confronted with GP33-specific CD8⁺ CTLs. Within 3 hours the neurites developed cytoskeleton breaks with adjacent solitary neuritic spheroids, as documented by confocal examination of the cytoskeletal marker ß-tubulin III. At the same time cytoskeleton staining of the neuronal somata showed no damage. The CTLs selectively attacked neurites and induced segmental membrane disruption 5 to 30 minutes after the establishment of peptide-specific CTL-neurite contact, as directly visualized by live confocal imaging. Thus, major histocompatibility complex class I/peptide-restricted CD8⁺ T lymphocytes can induce lesions to neurites, which might be responsible for axonal damage during neuroinflammatory diseases.

This article has been cited by other articles:

				R. Dutta and B. D. Trapp Pathogenesis of axonal and neuronal damage in multiple sclerosis Neurology, May 29, 2007; 68(22_suppl_3): S22 - S31. [Abstract] [Full Text] [PDF]

				I. Metz, C. F. Lucchinetti, H. Openshaw, A. Garcia-Merino, H. Lassmann, M. S. Freedman, H. L. Atkins, B. Azzarelli, O. J. Kolar, and W. Bruck Autologous haematopoietic stem cell transplantation fails to stop demyelination and neurodegeneration in multiple sclerosis Brain, May 1, 2007; 130(5): 1254 - 1262. [Abstract] [Full Text] [PDF]

				C. Wegner, M. M. Esiri, S. A. Chance, J. Palace, and P. M. Matthews Neocortical neuronal, synaptic, and glial loss in multiple sclerosis. Neurology, September 26, 2006; 67(6): 960 - 967. [Abstract] [Full Text] [PDF]

				L. P. Shriver and B. N. Dittel T-Cell-Mediated Disruption of the Neuronal Microtubule Network: Correlation with Early Reversible Axonal Dysfunction in Acute Experimental Autoimmune Encephalomyelitis Am. J. Pathol., September 1, 2006; 169(3): 999 - 1011. [Abstract] [Full Text] [PDF]

				M. Brisebois, S. P. Zehntner, J. Estrada, T. Owens, and S. Fournier A Pathogenic Role for CD8+ T Cells in a Spontaneous Model of Demyelinating Disease J. Immunol., August 15, 2006; 177(4): 2403 - 2411. [Abstract] [Full Text] [PDF]

				C. W. Ip, A. Kroner, M. Bendszus, C. Leder, I. Kobsar, S. Fischer, H. Wiendl, K.-A. Nave, and R. Martini Immune Cells Contribute to Myelin Degeneration and Axonopathic Changes in Mice Overexpressing Proteolipid Protein in Oligodendrocytes J. Neurosci., August 2, 2006; 26(31): 8206 - 8216. [Abstract] [Full Text] [PDF]

				R. Gold, C. Linington, and H. Lassmann Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research Brain, August 1, 2006; 129(8): 1953 - 1971. [Abstract] [Full Text] [PDF]

				T. Wang, R. Allie, K. Conant, N. Haughey, J. Turchan-Chelowo, K. Hahn, A. Rosen, J. Steiner, S. Keswani, M. Jones, et al. Granzyme B mediates neurotoxicity through a G-protein-coupled receptor FASEB J, June 1, 2006; 20(8): 1209 - 1211. [Abstract] [Full Text] [PDF]

				Y. Zhu, J. Antony, S. Liu, J. A. Martinez, F. Giuliani, D. Zochodne, and C. Power CD8+ lymphocyte-mediated injury of dorsal root ganglion neurons during lentivirus infection: CD154-dependent cell contact neurotoxicity. J. Neurosci., March 29, 2006; 26(13): 3396 - 3403. [Abstract] [Full Text] [PDF]

				E Fainardi, R Rizzo, L Melchiorri, M Castellazzi, E Paolino, M R Tola, E Granieri, and O R Baricordi Intrathecal synthesis of soluble HLA-G and HLA-I molecules are reciprocally associated to clinical and MRI activity in patients with multiple sclerosis Multiple Sclerosis, February 1, 2006; 12(1): 2 - 12. [Abstract] [PDF]

				I. Tsunoda, L.-Q. Kuang, M. Kobayashi-Warren, and R. S. Fujinami Central Nervous System Pathology Caused by Autoreactive CD8+ T-Cell Clones following Virus Infection J. Virol., December 1, 2005; 79(23): 14640 - 14646. [Abstract] [Full Text] [PDF]

				M. A. Friese and L. Fugger Autoreactive CD8+ T cells in multiple sclerosis: a new target for therapy? Brain, August 1, 2005; 128(8): 1747 - 1763. [Abstract] [Full Text] [PDF]

				D.-A. Laplaud, C. Ruiz, S. Wiertlewski, S. Brouard, L. Berthelot, M. Guillet, B. Melchior, N. Degauque, G. Edan, P. Brachet, et al. Blood T-cell receptor {beta} chain transcriptome in multiple sclerosis. Characterization of the T cells with altered CDR3 length distribution Brain, May 1, 2004; 127(5): 981 - 995. [Abstract] [Full Text] [PDF]

				T. B. Jones, D. P. Ankeny, Z. Guan, V. McGaughy, L. C. Fisher, D. M. Basso, and P. G. Popovich Passive or Active Immunization with Myelin Basic Protein Impairs Neurological Function and Exacerbates Neuropathology after Spinal Cord Injury in Rats J. Neurosci., April 14, 2004; 24(15): 3752 - 3761. [Abstract] [Full Text] [PDF]

				M. Rodriguez, L. J. Zoecklein, C. L. Howe, K. D. Pavelko, J. D. Gamez, S. Nakane, and L. M. Papke Gamma Interferon Is Critical for Neuronal Viral Clearance and Protection in a Susceptible Mouse Strain following Early Intracranial Theiler's Murine Encephalomyelitis Virus Infection J. Virol., November 15, 2003; 77(22): 12252 - 12265. [Abstract] [Full Text] [PDF]

				M Bradl and R Hohlfeld Molecular pathogenesis of neuroinflammation J. Neurol. Neurosurg. Psychiatry, October 1, 2003; 74(10): 1364 - 1370. [Abstract] [Full Text] [PDF]

				F. Giuliani, C. G. Goodyer, J. P. Antel, and V. W. Yong Vulnerability of Human Neurons to T Cell-Mediated Cytotoxicity J. Immunol., July 1, 2003; 171(1): 368 - 379. [Abstract] [Full Text] [PDF]

				H Lassmann Axonal injury in multiple sclerosis J. Neurol. Neurosurg. Psychiatry, June 1, 2003; 74(6): 695 - 697. [Full Text] [PDF]

				M. Rodriguez A function of myelin is to protect axons from subsequent injury: implications for deficits in multiple sclerosis Brain, April 1, 2003; 126(4): 751 - 752. [Full Text] [PDF]

				I. M. Medana and M. M. Esiri Axonal damage: a key predictor of outcome in human CNS diseases Brain, March 1, 2003; 126(3): 515 - 530. [Abstract] [Full Text] [PDF]