Beneficial effect of co-polymer 1 on cytokine production by CD4 T cells in multiple sclerosis

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Abstract
Multiple sclerosis (MS) has been associated with an imbalance in the T helper type 1 (Th1) and Th2 subsets. We investigated, at the single-cell level, the synthesis of pro-inflammatory cytokines by CD4 and CD8 T cells from MS patients. We report the relationship between priming of CD4 and CD8 T cells for interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) and disease evolution in MS patients, clinically subdivided into relapsing–remitting MS (RRMS) in remission, RRMS in relapse, or chronic progressive MS (CPMS). Moreover, we report the in vivo influence of co-polymer 1 (COP) treatment on the pattern of cytokine producers in RRMS patients. We show that the frequency of CD4 T cells primed for TNF-α synthesis increased in all stages of MS, including RRMS remitting, and was normalized to control values in COP-treated patients (43·2 ± 11·8% in treated patients versus 47 ± 7·3% in RRMS remitting versus 40·3 ± 8% in controls). In addition, a significant decrease in the frequency of CD4 T cells primed for IL-2 was found in COP-treated patients as compared to the other groups of patients, reaching values below that of controls (59·1 ± 9·9% in treated patients versus 70 ± 11·6% in RRMS remitting versus 67·1 ± 7·4% in controls). Unexpectedly, COP-treated patients also showed a significantly decreased priming for IFN-γ at the CD4 T-cell level (9·1 ± 3·4% in treated patients versus 18·8 ± 0·6.4% in RRMS remitting versus 15·4 ± 4·7% in controls), but not at the CD8 T-cell level. This bystander suppression on the inflammatory cells should be considered in the monitoring of MS patients submitted to COP treatment, in order to evaluate better its clinical efficacy.