Naturally occurring CD4+CD25+ regulatory T cells prevent but do not improve experimental myasthenia gravis.
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.
Nessi
Valeria
V
Neurology IV, Neurological Institute Foundation Carlo Besta, Milan, Italy.
Nava
Sara
S
Ruocco
Chiara
C
Toscani
Chiara
C
Mantegazza
Renato
R
Antozzi
Carlo
C
Baggi
Fulvio
F
D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018189:Immunomagnetic Separation; D016130:Immunophenotyping; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology*; D016133:Polymerase Chain Reaction; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D001323:Autoantibodies; D011950:Receptors, Cholinergic