RESUMO
The induction phase of experimental autoimmune encephalomyelitis (EAE) in mice is T cell dependent and coreceptors that regulate T cell activation modulate disease development. We report here that mice lacking CD5, an important modulator of T cell activation, exhibit significantly delayed onset and decreased severity of EAE. The resistance to EAE in CD5(-/-) mice was not due to the inability of T cells to respond efficiently to stimulation with MOG(35-55) but was associated with the presence of elevated frequency of apoptotic activated T cells in spleens and DLN. We also observed a net decrease in peripheral activated CD4(+) T cells in CD5(-/-) spleens and DLN 10 days after immunization. We further show that in vivo blockade of CD5 engagement after induction of EAE by soluble CD5-Fc, a treatment that induces elimination of activated T cells, promoted recovery from EAE. Our studies indicate that CD5 regulates survival of activated T cells and provides a target for treatment of T cell-dependent autoimmune diseases such as multiple sclerosis.
Assuntos
Antígenos CD5/imunologia , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/imunologia , Animais , Antígenos CD5/metabolismo , Antígenos CD5/uso terapêutico , Divisão Celular/efeitos dos fármacos , Divisão Celular/imunologia , Ligantes , Camundongos , Proteínas Serina-Treonina Quinases/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Timo/efeitos dos fármacos , Timo/imunologia , Fatores de TempoRESUMO
OBJECTIVE: To evaluate the efficacy of an anti-CD5 ricin-linked immunoconjugate (CD5-IC) in patients with rheumatoid arthritis (RA). METHODS: A total of 104 evaluable patients were enrolled in a multicenter, double-blind, multiple-dose, placebo-controlled study of CD5-IC. RESULTS: Treatment with CD5-IC in doses up to 8 mg/m2/day for 4 days in 1 month failed to produce marked or prolonged T cell depletion and was no more effective than placebo in ameliorating disease manifestations. An unexpectedly high placebo response was observed in 48% of the patients. Adverse events were correlated with the dose of CD5-IC, but the treatment was generally well-tolerated. CONCLUSION: At the doses used in this study, CD5-IC was ineffective for treating RA.
