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

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(+)CD25(high) 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.

• Authors: Valeria Nessi, Sara Nava, Chiara Ruocco, Chiara Toscani, Renato Mantegazza, Carlo Antozzi, Fulvio Baggi
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 185 Issue 9 Pg. 5656-67 (Nov 01 2010) ISSN: 1550-6606 [Electronic] United States
• PMID: 20881192 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Receptors, Cholinergic

Topics

• Animals
• Autoantibodies (blood, immunology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Immunomagnetic Separation
• Immunophenotyping
• Myasthenia Gravis, Autoimmune, Experimental (immunology)
• Polymerase Chain Reaction
• Rats
• Rats, Inbred Lew
• Receptors, Cholinergic (immunology)
• T-Lymphocytes, Regulatory (immunology)