| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Departments of Oncology and Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada;
McGill University, Montreal Children’s Hospital Research Institute, Montreal, Quebec, Canada; and
Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
Axonal and neuronal loss occurs in inflammatory diseases of the CNS such as multiple sclerosis. The cause of the loss remains unclear. We report that polyclonally activated T cells align along axons and soma of cultured human neurons leading to substantial neuronal death. This occurs in an allogeneic and syngeneic manner in the absence of added Ag, requires T cells to be activated, and is mediated through cell contact-dependent mechanisms involving FasL, LFA-1, and CD40 but not MHC class I. Activated CD4+ and CD8+ T cell subsets are equally neuronal cytotoxic. In contrast to neurons, other CNS cell types (oligodendrocytes and astrocytes) are not killed by T cells. These results demonstrate for the first time the high and selective vulnerability of human neurons to T cells, and suggest that when enough activated T cells accumulate in the CNS, neuronal cytotoxicity can result through Ag-independent non-MHC class I mechanisms.
This article has been cited by other articles:
|
|
 |
|
  V. W. Yong and S. Marks The interplay between the immune and central nervous systems in neuronal injury Neurology, January 5, 2010; 74(1_Supplement_1): S9 - S16. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Melzer, S. G. Meuth, and H. Wiendl CD8+ T cells and neuronal damage: direct and collateral mechanisms of cytotoxicity and impaired electrical excitability FASEB J, November 1, 2009; 23(11): 3659 - 3673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Huizinga, R. Q. Hintzen, K. Assink, M. van Meurs, and S. Amor T-cell responses to neurofilament light protein are part of the normal immune repertoire Int. Immunol., April 1, 2009; 21(4): 433 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Brunn, O. Utermohlen, M. Carstov, M. S. Ruiz, H. Miletic, D. Schluter, and M. Deckert CD4 T Cells Mediate Axonal Damage and Spinal Cord Motor Neuron Apoptosis in Murine P0106-125-Induced Experimental Autoimmune Neuritis Am. J. Pathol., July 1, 2008; 173(1): 93 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Tian, J. Lappalainen, M. Autero, S. Hanninen, H. Rauvala, and C. G. Gahmberg Shedded neuronal ICAM-5 suppresses T-cell activation Blood, April 1, 2008; 111(7): 3615 - 3625. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. P. Greene, E.-Y. Lee, N. Prow, B. Ngwang, and D. E. Griffin Protection from fatal viral encephalomyelitis: AMPA receptor antagonists have a direct effect on the inflammatory response to infection PNAS, March 4, 2008; 105(9): 3575 - 3580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
V. W. Yong, F. Giuliani, M. Xue, A. Bar-Or, and L. M. Metz Experimental models of neuroprotection relevant to multiple sclerosis Neurology, May 29, 2007; 68(22_suppl_3): S32 - S37. [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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 J. Imitola, T. Chitnis, and S. J. Khoury Insights Into the Molecular Pathogenesis of Progression in Multiple Sclerosis: Potential Implications for Future Therapies Arch Neurol, January 1, 2006; 63(1): 25 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Giuliani, W. Hader, and V. W. Yong Minocycline attenuates T cell and microglia activity to impair cytokine production in T cell-microglia interaction J. Leukoc. Biol., July 1, 2005; 78(1): 135 - 143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Noorbakhsh, N. Vergnolle, J. C. McArthur, C. Silva, M. Vodjgani, P. Andrade-Gordon, M. D. Hollenberg, and C. Power Proteinase-Activated Receptor-2 Induction by Neuroinflammation Prevents Neuronal Death during HIV Infection J. Immunol., June 1, 2005; 174(11): 7320 - 7329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Ruffini, T. E. Kennedy, and J. P. Antel Inflammation and Remyelination in the Central Nervous System: A Tale of Two Systems Am. J. Pathol., May 1, 2004; 164(5): 1519 - 1522. [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]
|
|
|
|
|
|
R. Nitsch, E. E. Pohl, A. Smorodchenko, C. Infante-Duarte, O. Aktas, and F. Zipp Direct Impact of T Cells on Neurons Revealed by Two-Photon Microscopy in Living Brain Tissue J. Neurosci., March 10, 2004; 24(10): 2458 - 2464. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
