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Treatment of recipient mice with the proteasome inhibitor N<jats:sup>\u03b1<\/jats:sup>\u2010benzyloxycarbonyl\u2010l\u2010leucyl\u2010l\u2010leucyl\u2010l\u2010leucinal (MG132) resulted in a 76% reduction in transfer\u2010induced diabetes. The closely related inhibitor carbobenzoxy\u2010l\u2010leucyl\u2010l\u2010leucinal that inhibits calpains but not the proteasome had no protective effect, suggesting that MG132 acted via inhibition of the proteasome. MG132 decreased proliferation of transferred T cells in the pancreatic lymph nodes <jats:italic>in vivo<\/jats:italic> and prevented their expansion in a dose\u2010dependent manner <jats:italic>in vitro<\/jats:italic>, consistent with a direct effect by MG132 on the T cells. MG132 did not prevent migration of transferred T cells into the islets but reduced the number of mice with severe infiltration. We suggest that MG132 prevents transfer\u2010induced diabetes by directly targeting the autoreactive T cells and lowering their diabetogenic potential.<\/jats:p>","DOI":"10.1111\/j.0300-9475.2004.01473.x","type":"journal-article","created":{"date-parts":[[2004,7,5]],"date-time":"2004-07-05T19:20:35Z","timestamp":1089055235000},"page":"134-142","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Inhibition of the Proteasome Reduces Transfer\u2010Induced Diabetes in Nonobese Diabetic 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