Development of spontaneous autoimmune peripheral polyneuropathy in B7-2-deficient NOD mice

An increasing number of studies have documented the central role of T cell costimulation in autoimmunity. Here we show that the autoimmune diabetes-pr one 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 li mb paralysis with histologic and electrophysiologic evidence of severe demy elination in the peripheral nerves beginning at 20 wk of age. No central ne rvous system lesions were apparent. The peripheral nerve tissue was infiltr ated with dendritic cells, CD4(+), and CD8(+) T cells. Finally, CD4(+) T ce lls isolated from affected animals induced the disease in NOD.SCID mice. Th us, the B7-2-deficient NOD mouse constitutes the first model of a spontaneo us autoimmune disease of the peripheral nervous system, which has many simi larities to the human disease, chronic inflammatory demyelinating polyneuro pathy (CIDP). This model demonstrates that NOD mice have "cryptic" autoimmu ne defects that can polarize toward the nervous tissue after the selective disruption of CD28/B7-2 costimulatory pathway.