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Biol Pharm Bull ; 38(8): 1120-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25994913

RESUMO

We previously reported that combination treatment with fingolimod (FTY720) plus antigenic peptide of glucose-6-phosphate isomerase (residues 325-339) (GPI325-339) from the onset of symptoms significantly inhibited disease progression in a mouse model of GPI325-339-induced arthritis. In this study, we investigated the mechanism(s) involved. The model mice were treated from arthritis onset with FTY720 alone, GPI325-339 alone, or the combination of FTY720 plus GPI325-339. At the end of treatment, inguinal lymph nodes (LNs) were excised and examined histologically and in flow cytometry. Levels of apoptotic cells, programmed death-1-expressing CD4(+)forkhead box P3(-) nonregulatory T cells (non-Tregs), and cytotoxic T-lymphocyte antigen 4-expressing non-Tregs in inguinal LNs were markedly increased in the combination treatment group mice. Regulatory T cells (Tregs) were also increased. These results indicate that combination treatment with FTY720 plus GPI325-339 inhibits the progression of arthritis by inducing clonal deletion and anergy of pathogenic T cells and also by immune suppression via Tregs.


Assuntos
Antígenos , Artrite Experimental , Artrite Reumatoide , Cloridrato de Fingolimode/farmacologia , Glucose-6-Fosfato Isomerase , Tolerância Imunológica/efeitos dos fármacos , Imunossupressores/farmacologia , Animais , Antígenos/imunologia , Antígenos/farmacologia , Antígenos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Experimental/imunologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Linfócitos T CD4-Positivos/metabolismo , Terapia Combinada , Modelos Animais de Doenças , Progressão da Doença , Cloridrato de Fingolimode/uso terapêutico , Glucose-6-Fosfato Isomerase/imunologia , Glucose-6-Fosfato Isomerase/farmacologia , Glucose-6-Fosfato Isomerase/uso terapêutico , Imunossupressores/uso terapêutico , Masculino , Camundongos Endogâmicos DBA , Peptídeos/imunologia , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Linfócitos T Reguladores/metabolismo
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