The Journal of Experimental Medicine
IN Cell Analyzer 2000
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Published online 3 September 2001. doi:10.1084/jem.194.5.677
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© The Rockefeller University Press, 0022-1007/2001/9/677/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 5, September 3, 2001 677-684

Original Article

Development of Spontaneous Autoimmune Peripheral Polyneuropathy in B7-2–Deficient Nod Mice

Benoît Salomona,b, Lesley Rheea,b, Helene Bour-Jordana,b,e, Honor Hsine, Anthony Montagc, Betty Solivend, Jennifer Arcellaa,b, Ann M. Girvinf, Stephen D. Millerf, and Jeffrey A. Bluestonea,b,c,e

a The Committee on Immunology, University of Chicago, Chicago, IL 60637
b Ben May Institute for Cancer Research, University of Chicago, Chicago, IL 60637
c Department of Pathology, University of Chicago, Chicago, IL 60637
d Department of Neurology, University of Chicago, Chicago, IL 60637
e University of California San Francisco Diabetes Center, University of California San Francisco, San Francisco, CA 94143
f Department of Immunology and Microbiology, Northwestern University, Chicago, IL 60611
UCSF Diabetes Center, University of California, San Francisco, 513 Parnassus Ave., Box 0540, San Francisco, CA 94143.415-476-1660415-514-1683

jbluest{at}diabetes.ucsf.edu

An increasing number of studies have documented the central role of T cell costimulation in autoimmunity. Here we show that the autoimmune diabetes-prone nonobese diabetic (NOD) mouse strain, deficient in B7-2 costimulation, is protected from diabetes but develops a spontaneous autoimmune peripheral polyneuropathy. All the female and one third of the male mice exhibited limb paralysis with histologic and electrophysiologic evidence of severe demyelination in the peripheral nerves beginning at 20 wk of age. No central nervous system lesions were apparent. The peripheral nerve tissue was infiltrated with dendritic cells, CD4+, and CD8+ T cells. Finally, CD4+ T cells isolated from affected animals induced the disease in NOD.SCID mice. Thus, the B7-2–deficient NOD mouse constitutes the first model of a spontaneous autoimmune disease of the peripheral nervous system, which has many similarities to the human disease, chronic inflammatory demyelinating polyneuropathy (CIDP). This model demonstrates that NOD mice have "cryptic" autoimmune defects that can polarize toward the nervous tissue after the selective disruption of CD28/B7-2 costimulatory pathway.

Key Words: autoimmunity • peripheral neuropathy • B7-2 costimulation • animal model • NOD mice

Abbreviations used in this paper: CIDP, chronic inflammatory demyelinating polyneuropathy; CNS, central nervous system; KO, knockout; SAPP, spontaneous autoimmune peripheral polyneuropathy; WT, wild-type.

B. Salomon's present address is Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, Centre National de la Recherche Scientifique ESA 7087, CERVI, Hôpital de la Pitié-Salpêtrière, Paris 75013, France.

© 2001 The Rockefeller University Press


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