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International Immunology, Vol. 15, No. 10, pp. 1173-1181, October 2003
© 2003 Japanese Society for Immunology

Lack of patent liver autoimmunity after breakage of tolerance in a mouse model

Giovanna Del Pozzo1, Dina Mascolo1, Antonella Prisco1, Pasquale Barba1, Annamaria Anzisi2 and John Guardiola1

1 Institute of Genetics and Biophysics ‘A. Buzzati Traverso’, via G. Marconi 10, 80125, Naples, Italy 2 Department of Oncology, National Institute for Cancer Research, Via M. Semmola, 80131 Naples, Italy

Correspondence to: G. Del Pozzo; E-mail: delpozzo{at}iigb.na.cnr.it
Transmitting editor: I. Pecht

We report in this work that a cellular and humoral autoreactive response can be induced against liver-specific self-determinants by repeated immunization with a chimeric tissue-specific self-antigen carrying a heterologous Th epitope. Epitope spreading rendering the autoimmune reaction independent of the presence of the cognate heterologous help is also demonstrated. Although neutrophil infiltrates can be demonstrated in the livers of treated mice, no clinical sign of organ damage is observed. These findings suggest that breakage of tolerance by this means leads the process only up to the next checkpoint in the progression of autoimmune disease and that further events are required to precipitate functional organ impairment.

Keywords: epitope spreading, glutathione-S-transferase, liver autoimmunity, self-reactivity, Th


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