TY - JOUR
T1 - Naturally occurring CD4+CD25+ regulatory T cells prevent but do not improve experimental myasthenia gravis
AU - Nessi, Valeria
AU - Nava, Sara
AU - Ruocco, Chiara
AU - Toscani, Chiara
AU - Mantegazza, Renato
AU - Antozzi, Carlo
AU - Baggi, Fulvio
PY - 2010/11/1
Y1 - 2010/11/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.0903183
DO - 10.4049/jimmunol.0903183
M3 - Article
C2 - 20881192
AN - SCOPUS:78149484705
VL - 185
SP - 5656
EP - 5667
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 9
ER -