| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Neurology, The University of Chicago, Chicago, IL 60637
Elimination of the costimulatory molecule B7-2 prevents autoimmune diabetes in NOD mice, but leads to the development of a spontaneous autoimmune polyneuropathy (SAP), which resembles the human disease chronic inflammatory demyelinating polyneuropathy (CIDP). In this study, we examined the immunopathogenic mechanisms in this model, including identification of SAP Ags. We found that B7-2-deficient NOD mice exhibit changes in cytokine and chemokine gene expression in spleens over time. There was an increase in IL-17 and a decrease in IL-10 transcript levels at 4 mo (preclinical phase), whereas IFN-
expression peaked at 8 mo (clinical phase). There was also an increase in transcript levels of Th1 cytokines, CXCL10, and RANTES in sciatic nerves of mice that developed SAP. Splenocytes from SAP mice exhibited proliferative and Th1 cytokine responses to myelin P0 (180–199), but not to other P0 peptides or P2 (53–78). Adoptive transfer of P0-reactive T cells generated from SAP mice induced neuropathy in four of six NOD.SCID mice. Data from i.v. tolerance studies indicate that myelin P0 is one of the autoantigens targeted by T cells in SAP in this model. The expression of P0 by peri-islet Schwann cells provides a potential mechanism linking islet autoimmunity and inflammatory neuropathy.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Grant R21 NS049014 from the National Institutes of Health, by a pilot grant from the GBS/CIDP Foundation International, Miller Group Charitable Trust Fund (M. P. Miller III), and Jack Miller Center for Peripheral Neuropathy.
2 H.-J.K. and C.-G.J. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Betty Soliven, Department of Neurology, MC2030, The University of Chicago; 5841 South Maryland Avenue, Chicago, IL 60637. E-mail address: bsoliven{at}neurology.bsd.uchicago.edu
4 Abbreviations used in this paper: SAP, spontaneous autoimmune polyneuropathy; CIDP, chronic inflammatory demyelinating polyneuropathy; PNS, peripheral nervous system; EAN, experimental autoimmune neuritis; GFAP, glial fibrillary acid protein; KO, knockout; P0, myelin protein zero; Treg, regulatory T cell; WT, wild type.
5 The online version of this article contains supplemental material.
This article has been cited by other articles:
|
|
 |
|
  C. Louvet, B. G. Kabre, D. W. Davini, N. Martinier, M. A. Su, J. J. DeVoss, W. L. Rosenthal, M. S. Anderson, H. Bour-Jordan, and J. A. Bluestone A novel myelin P0-specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy J. Exp. Med., March 16, 2009; 206(3): 507 - 514. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
