| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Center for Neurologic Diseases, Department of Neurology, and
Vascular Research Division, Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115;
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138; and
§
Department of Neurology, University of California, San Francisco, CA 94143
Astrocytes are nonprofessional APCs that may participate in Ag
presentation and activation of pathogenic CD4+ T cells
involved in central nervous system (CNS) inflammatory diseases. Using
immortalized pure astrocytes as a complement to the study of primary
astrocytes, we investigated whether these astrocytes express elements
involved in the class II endocytic pathway and if they are capable of
processing native myelin basic protein (MBP), a step that could be
necessary for initiating or perpetuating T cell recognition of this
self-Ag in vivo. Upon IFN-
-stimulation, primary and immortalized
astrocytes up-regulate class II transactivator (CIITA), invariant chain
(Ii) (p31 and p41), H-2Ma, and H-2Mb. Analysis of CIITA cDNA sequences
demonstrated that CIITA transcription in astrocytes is directed by a
promoter (type IV) that mediates IFN--inducible CIITA expression and
encodes a CIITA protein that differs in its N-terminal sequence from
CIITA reported in professional APC. Comparing live and fixed APC for Ag
presentation, we show that Ag processing by APC is required for
presentation of native MBP to autopathogenic T cells specific for the
major MBP epitope, Ac1-11. We have observed that primary astrocytes and
some, but not all, astrocyte lines in the absence of contaminating
microglia are capable of processing and presenting native MBP,
suggesting that there may be heterogeneity. Our study provides
definitive evidence that astrocytes are capable of processing CNS
autoantigen, indicating that astrocytes have potential for processing
and presentation of CNS autoantigen to proinflammatory T cells in CNS
autoimmune disease.
This article has been cited by other articles:
|
|
 |
|
  R. Arakaki, A. Nagaoka, N. Ishimaru, A. Yamada, S. Yoshida, and Y. Hayashi Role of Plasmacytoid Dendritic Cells for Aberrant Class II Expression in Exocrine Glands from Estrogen-Deficient Mice of Healthy Background Am. J. Pathol., May 1, 2009; 174(5): 1715 - 1724. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Jiang, Y. Ke, D. Sun, G. Han, H. J. Kaplan, and H. Shao Reactivation of Uveitogenic T Cells by Retinal Astrocytes Derived from Experimental Autoimmune Uveitis-Prone B10RIII Mice Invest. Ophthalmol. Vis. Sci., January 1, 2008; 49(1): 282 - 289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Tezel, X. Yang, C. Luo, Y. Peng, S. L. Sun, and D. Sun Mechanisms of Immune System Activation in Glaucoma: Oxidative Stress-Stimulated Antigen Presentation by the Retina and Optic Nerve Head Glia Invest. Ophthalmol. Vis. Sci., February 1, 2007; 48(2): 705 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. C. Hornell, G. W. Beresford, A. Bushey, J. M. Boss, and E. D. Mellins Regulation of the Class II MHC Pathway in Primary Human Monocytes by Granulocyte-Macrophage Colony-Stimulating Factor J. Immunol., September 1, 2003; 171(5): 2374 - 2383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.-Y. Dietrich, P. R. Walker, and P. Saas Death receptors on reactive astrocytes: A key role in the fine tuning of brain inflammation? Neurology, February 25, 2003; 60(4): 548 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. De Keyser, E. Zeinstra, and E. Frohman Are Astrocytes Central Players in the Pathophysiology of Multiple Sclerosis? Arch Neurol, January 1, 2003; 60(1): 132 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Stuve, S. Youssef, A. J. Slavin, C. L. King, J. C. Patarroyo, D. L. Hirschberg, W. J. Brickey, J. M. Soos, J. F. Piskurich, H. A. Chapman, et al. The Role of the MHC Class II Transactivator in Class II Expression and Antigen Presentation by Astrocytes and in Susceptibility to Central Nervous System Autoimmune Disease J. Immunol., December 15, 2002; 169(12): 6720 - 6732. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Cornet, T. C. Savidge, J. Cabarrocas, W.-L. Deng, J.-F. Colombel, H. Lassmann, P. Desreumaux, and R. S. Liblau Enterocolitis induced by autoimmune targeting of enteric glial cells: A possible mechanism in Crohn's disease? PNAS, October 25, 2001; (2001) 231474098. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Krogsgaard, K. W. Wucherpfennig, B. Canella, B. E. Hansen, A. Svejgaard, J. Pyrdol, H. Ditzel, C. Raine, J. Engberg, and L. Fugger Visualization of Myelin Basic Protein (MBP) T Cell Epitopes in Multiple Sclerosis Lesions using a Monoclonal Antibody Specific for the Human Histocompatibility Leukocyte Antigen (HLA)-DR2-MBP 85-99 Complex J. Exp. Med., April 18, 2000; 191(8): 1395 - 1412. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Soos, T. A. Ashley, J. Morrow, J. C. Patarroyo, B. E. Szente, and S. S. Zamvil Differential expression of B7 co-stimulatory molecules by astrocytes correlates with T cell activation and cytokine production Int. Immunol., July 1, 1999; 11(7): 1169 - 1179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cornet, T. C. Savidge, J. Cabarrocas, W.-L. Deng, J.-F. Colombel, H. Lassmann, P. Desreumaux, and R. S. Liblau Enterocolitis induced by autoimmune targeting of enteric glial cells: A possible mechanism in Crohn's disease? PNAS, November 6, 2001; 98(23): 13306 - 13311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Girvin, K. B. Gordon, C. J. Welsh, N. A. Clipstone, and S. D. Miller Differential abilities of central nervous system resident endothelial cells and astrocytes to serve as inducible antigen-presenting cells Blood, May 15, 2002; 99(10): 3692 - 3701. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
