| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Immunology and
Neurology, Mayo Clinic, Rochester, MN 55905
Intracranial infection of susceptible mice with Theiler’s virus results in persistent infection and spinal cord demyelination similar to human multiple sclerosis. While central nervous system infiltrating lymphocytes (CNS-ILs) in these mice display no virus-specific CTL activity, the cells were found to be activated killers using a specificity-independent assay. We previously demonstrated that the depletion of T cells in persistently infected mice significantly decreases demyelinating disease. Consequently, we have investigated the killing pathways employed by CNS-ILs that are isolated from persistently infected animals, the relative contribution of CD4 and CD8 cells in the generation of these CTLs, and the reactivity of this cell population to two putative autoantigens in the CNS. In vitro or in vivo manipulation of T cell populations using Abs or genetic knockout strategies demonstrate that the cytotoxic activity is primarily mediated by CD8+ T cells, and that perforin is an important molecule in the effector pathway. Since effector functions in infected mice were not inhibited by the depletion of CD4 cells with mAb but was blocked genetically in CD4 knockout mice, CD4+ T cells appear to play a helper role in the generation of CD8+ CTLs. We found no evidence of autoimmune-mediated demyelination, as the CD8+ CTLs were not reactive to two major myelin autoantigens, myelin basic protein and proteolipid protein. Our finding that CNS-ILs that are isolated from mice susceptible to persistent virus infection are neither specific for virus or myelin autoantigens is consistent with the possibility that CD8+ CTLs mediate CNS damage as a result of nonspecific activation by virus.
This article has been cited by other articles:
|
|
 |
|
  M. Rodriguez, L. Zoecklein, J. G. Kerkvliet, K. D. Pavelko, L. Papke, C. L. Howe, L. R. Pease, and C. David Human HLA-DR Transgenes Protect Mice from Fatal Virus-Induced Encephalomyelitis and Chronic Demyelination J. Virol., April 1, 2008; 82(7): 3369 - 3380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Ure, T. E. Lane, M. T. Liu, and M. Rodriguez Neutralization of chemokines RANTES and MIG increases virus antigen expression and spinal cord pathology during Theiler's virus infection Int. Immunol., May 1, 2005; 17(5): 569 - 579. [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]
|
|
|
|
|
|
I. Tsunoda, L.-Q. Kuang, and R. S. Fujinami Induction of Autoreactive CD8+ Cytotoxic T Cells during Theiler's Murine Encephalomyelitis Virus Infection: Implications for Autoimmunity J. Virol., November 13, 2002; 76(24): 12834 - 12844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-S. Kang, M. A. Lyman, and B. S. Kim The Majority of Infiltrating CD8+ T Cells in the Central Nervous System of Susceptible SJL/J Mice Infected with Theiler's Virus Are Virus Specific and Fully Functional J. Virol., June 5, 2002; 76(13): 6577 - 6585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Redwine, M. J. Buchmeier, and C. F. Evans In Vivo Expression of Major Histocompatibility Complex Molecules on Oligodendrocytes and Neurons during Viral Infection Am. J. Pathol., October 1, 2001; 159(4): 1219 - 1224. [Abstract] [Full Text]
|
|
|
|
|
|
M. Trottier, P. Kallio, W. Wang, and H. L. Lipton High Numbers of Viral RNA Copies in the Central Nervous System of Mice during Persistent Infection with Theiler's Virus J. Virol., August 15, 2001; 75(16): 7420 - 7428. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. D. Murray, D. B. McGavern, S. Sathornsumetee, and M. Rodriguez Spontaneous remyelination following extensive demyelination is associated with improved neurological function in a viral model of multiple sclerosis Brain, July 1, 2001; 124(7): 1403 - 1416. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Wu, Y. Sun, J. Wang, X. Lin, Y. Wang, L. E. Pegg, A. Futterer, K. Pfeffer, and Y.-X. Fu Signal Via Lymphotoxin-{{beta}}R on Bone Marrow Stromal Cells Is Required for an Early Checkpoint of NK Cell Development J. Immunol., February 1, 2001; 166(3): 1684 - 1689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Drescher, P. D. Murray, X. Lin, J. A. Carlino, and M. Rodriguez TGF-{beta}2 Reduces Demyelination, Virus Antigen Expression, and Macrophage Recruitment in a Viral Model of Multiple Sclerosis J. Immunol., March 15, 2000; 164(6): 3207 - 3213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Bergmann, J. D. Altman, D. Hinton, and S. A. Stohlman Inverted Immunodominance and Impaired Cytolytic Function of CD8+ T Cells During Viral Persistence in the Central Nervous System J. Immunol., September 15, 1999; 163(6): 3379 - 3387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Perrin, V. Schnuriger, A.-L. Quiquerez, P. Saas, C. Pannetier, N. de Tribolet, J.-M. Tiercy, J.-P. Aubry, P.-Y. Dietrich, and P. R. Walker Astrocytoma infiltrating lymphocytes include major T cell clonal expansions confined to the CD8 subset Int. Immunol., August 1, 1999; 11(8): 1337 - 1350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Johnson, M. K. Njenga, M. J. Hansen, S. T. Kuhns, L. Chen, M. Rodriguez, and L. R. Pease Prevalent Class I-Restricted T-Cell Response to the Theiler's Virus Epitope Db:VP2121-130 in the Absence of Endogenous CD4 Help, Tumor Necrosis Factor Alpha, Gamma Interferon, Perforin, or Costimulation through CD28 J. Virol., May 1, 1999; 73(5): 3702 - 3708. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
