Deferiprone modulates in vitro responses by peripheral blood T cells from control and relapsing–remitting multiple sclerosis subjects

T cells are important mediators of autoimmune inflammation in relapsing–remitting multiple sclerosis (RRMS). Previous studies found that deferiprone, an iron chelator, suppressed disease activity in a mouse model of multiple sclerosis, and inhibition of T cell proliferation was implicated as a putat...

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Veröffentlicht in:International immunopharmacology 2011-11, Vol.11 (11), p.1796-1801
Hauptverfasser: Sweeney, Matthew E., Slusser, Joyce G., Lynch, Sharon G., Benedict, Stephen H., Garcia, Sharon L., Rues, Laura, LeVine, Steven M.
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Sprache:eng
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Zusammenfassung:T cells are important mediators of autoimmune inflammation in relapsing–remitting multiple sclerosis (RRMS). Previous studies found that deferiprone, an iron chelator, suppressed disease activity in a mouse model of multiple sclerosis, and inhibition of T cell proliferation was implicated as a putative mechanism. The objective of the present study was to examine the effects of deferiprone on suppressing in vitro responses of T cells from control and RRMS subjects. Peripheral blood T cells were co-stimulated with anti-CD3+anti-CD28 and cultured with or without interleukin 2 (IL-2). Proliferating CD4+ T cells from control and RRMS subjects, cultured with or without IL-2, decreased in response to 75μM deferiprone, although the extent of decreased proliferation of CD4+ T cells from RRMS subjects was less than for control subjects. Proliferating CD8+ T cells from control subjects, cultured with or without IL-2, also decreased in response to 75μM deferiprone, and this decrease was seen in proliferating CD8+ T cells from RRMS cultured with IL-2. CD4+CD25+ and CD8+CD25+ cells from control subjects, cultured with or without IL-2, declined in 75μM deferiprone, but the decrease was smaller than for the CD4+ and CD8+ proliferative responses. CD4+CD25+ and CD8+CD25+ cells from RRMS subjects showed more variability than for control subjects, but CD4+CD25+ cultured with IL-2 and CD8+CD25+ cells cultured without IL-2 significantly declined in 75μM deferiprone. CD4+FoxP3+ and CD4+CD25+FoxP3+ cells tended to remain constant or increase. In summary, deferiprone induced declines in proliferative responses at a dosage that is within peak serum pharmacological concentrations. ► Deferiprone is a potential treatment for relapsing–remitting multiple sclerosis. ► Deferiprone was applied to T cells collected from RRMS or control subjects. ► T cell proliferation decreased in response to pharmacological levels of deferiprone. ► CD4+CD25+ and CD8+CD25+ cells declined in the presence of deferiprone. ► The findings are relevant for studies on the role of this drug in RRMS subjects.
ISSN:1567-5769
1878-1705
DOI:10.1016/j.intimp.2011.07.007