Naturally occurring CD4+CD25+ regulatory T cells prevent but do not improve experimental myasthenia gravis

Valeria Nessi, Sara Nava, Chiara Ruocco, Chiara Toscani, Renato Mantegazza, Carlo Antozzi, Fulvio Baggi

Research output: Contribution to journalArticlepeer-review

Abstract

In the current study, we investigated whether naturally occurring CD4 +CD25+ T cells, separated by immunomagnetic anti-CD4 and anti-CD25 Abs from naive animals, are able to protect from experimental autoimmune myasthenia gravis (EAMG) and modify the progression of ongoing disease when administered to Torpedo californica acetylcholine receptor (AChR)-immunized Lewis rats. 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 97-116 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.

Original languageEnglish
Pages (from-to)5656-5667
Number of pages12
JournalJournal of Immunology
Volume185
Issue number9
DOIs
Publication statusPublished - Nov 1 2010

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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