We assessed novel approaches to induce transgenic T-cell-receptor (TCR) experimental autoimmune neuritis (EAN) in mice to enhance translational research for inflammatory peripheral neuropathies (IPN).

The contribution of neuritogenic T-cells in the immunopathogenesis of IPN remains incompletely understood. Transgenic TCR-EAN mouse models have not been established yet. Toben et al generated transgenic mice with Schwann cell (SC) restricted Ovalbumin (Ova) expression as a model antigen in the peripheral nervous system (PNO mice). Yet, Ova based EAN induction in PNO mice was unsuccessful, implying mechanisms of immune tolerance.

OTII mice with Ova specific CD4-T-cells, PNO mice with Ova transgene insertion downstream SC regulatory elements and C57BL/6 mice (control) were used. EAN was passively induced by intraperitoneal transfer of naive OTII splenocytes into 14-days-old PNO or OTII/PNO mice. Disease severity was assessed daily. At experiment termination on day 16 post transfer the peripheral immune activation was analyzed via flow cytometry. Peripheral nervous system inflammation was characterized in sciatic nerve on electrophysiological-, histological-, and mRNA basis via quantitative real-time PCR.

After transfer of OTII-CD4-T-cells, PNO and OTII/PNO recipients developed proximal dominant clinical neuritis symptoms, which were underlined by prolonged or even absent F-wave latencies of the sciatic nerve. Flow cytometric analyses revealed a concurrent anti-inflammatory/regulatory immune phenotype in OTII/PNO recipients combined by milder EAN signs. Histological analyses of the sciatic nerves revealed an increased T cell inflammatory infiltration.

Adoptive transfer of OTII-CD4-T-cells induces proximal pronounced clinical EAN symptoms in TCR transgenic PNO and OTII/PNO recipients. On molecular level PNO and OTII/PNO mice acquired distinct immunological phenotypes with immune tolerance mechanisms for the OTII/PNO mice.