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Even though CD4+CD25+ and CD4+CD25high T cell frequencies were similar in the spleens and lymph nodes of EAMG and healthy rats, we observed that CD4+CD25+ T cells isolated from the spleens of naive animals inhibited in vitro the Ag-induced proliferation of T cell lines specific to the self-peptide 97\u2013116 of the anti-AChR subunit (R97-116), an immunodominant and myasthenogenic T cell epitope, whereas CD4+CD25+ T cells purified from the spleens of EAMG rats were less effective. CD4+CD25+ T cells from EAMG rats expressed less forkhead box transcription factor P3 but more CTLA-4 mRNA than healthy rats. Naive CD4+CD25+ T cells, obtained from naive rats and administered to T. californica AChR-immunized animals according to a preventive schedule of treatment, reduced the severity of EAMG, whereas their administration 4 wk postinduction of the disease, corresponding to the onset of clinical symptoms (therapeutic treatment), was not effective. We think that the exogenous administration of CD4+CD25+ naive T cells prevents the early events underlying the induction of EAMG, events linked to the T cell compartment (Ag recognition, epitope spreading, and T cell expansion), but fails to ameliorate ongoing EAMG, when the IgG-mediated complement attack to the AChR at the neuromuscular junction has already taken place.<\/jats:p>","DOI":"10.4049\/jimmunol.0903183","type":"journal-article","created":{"date-parts":[[2010,9,30]],"date-time":"2010-09-30T03:40:16Z","timestamp":1285818016000},"page":"5656-5667","source":"Crossref","is-referenced-by-count":21,"title":["Naturally Occurring CD4+CD25+ Regulatory T Cells Prevent but Do Not Improve Experimental Myasthenia Gravis"],"prefix":"10.1093","volume":"185","author":[{"given":"Valeria","family":"Nessi","sequence":"first","affiliation":[{"name":"Neurology IV, Neurological Institute Foundation \u201cCarlo Besta,\u201d \u00a0 20133 Milan ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Nava","sequence":"additional","affiliation":[{"name":"Neurology IV, Neurological Institute Foundation \u201cCarlo Besta,\u201d \u00a0 20133 Milan ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Ruocco","sequence":"additional","affiliation":[{"name":"Neurology IV, Neurological Institute Foundation \u201cCarlo Besta,\u201d \u00a0 20133 Milan ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Toscani","sequence":"additional","affiliation":[{"name":"Neurology IV, Neurological Institute Foundation \u201cCarlo Besta,\u201d \u00a0 20133 Milan ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renato","family":"Mantegazza","sequence":"additional","affiliation":[{"name":"Neurology IV, Neurological Institute Foundation \u201cCarlo Besta,\u201d \u00a0 20133 Milan ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Antozzi","sequence":"additional","affiliation":[{"name":"Neurology IV, Neurological Institute Foundation \u201cCarlo Besta,\u201d \u00a0 20133 Milan ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fulvio","family":"Baggi","sequence":"additional","affiliation":[{"name":"Neurology IV, Neurological Institute Foundation \u201cCarlo Besta,\u201d \u00a0 20133 Milan ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2010,11,1]]},"reference":[{"key":"2025032412060073600_r1","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/nri916","article-title":"Unravelling the pathogenesis of myasthenia gravis","volume":"2","author":"Vincent","year":"2002","journal-title":"Nat. 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