IFNbeta-1a therapy for multiple sclerosis expands regulatory CD8+ T cells and decreases memory CD8+ subset: a longitudinal 1-year study.

The beneficial effects of interferon beta-1a (IFNbeta-1a) in multiple sclerosis (MS) remain only partially understood. CD8(+) T cells are key cells in MS pathogenesis that contribute to axonal damage in MS, whereas CD4(+) regulatory T cells (T(Reg)) and CD8(+) regulatory/suppressor T cells (Ts) play an important role in protecting against subsequent MS activity. We analysed ex vivo changes on T(Reg) and on the different subsets of CD4(+) and CD8(+) T lymphocytes, before IFNbeta-1a (Rebif) therapy and at 3, 6, and 12 months after treatment, in 23 MS patients and in 26 healthy controls. IFNbeta-1a significantly increased the proportions of CD4(+) T(Reg) and regulatory CD8(+) T cells (Tr). Memory CD8(+) T cells were significantly decreased after 1 year of treatment, maybe reflecting down-regulation of abnormally persistent systemic activation in MS patients. After 1 year of IFNbeta-1a, a direct correlation was observed between plasmacytoid dendritic cells and effector CD8(+) T cells.

Clinical response to interferon-beta-1a may be linked to low baseline circulating BDCA1 myeloid dendritic cells Differential role of circulating dendritic cells and CD4+ regulatory T-cells in relapsing-remitting multiple sclerosis: a 1-year longitudinal study.

Many variables with association with better response to interferon-beta-1a (IFNbeta-1a) have been described, but none has yet been shown to be predictive of clinical response. In this real-life observational 1-year longitudinal study of 23 relapsing-remitting multiple sclerosis (RRMS) patients treated with subcutaneous IFNbeta-1a, we have shown a lower proportion of circulating myeloid dendritic cells (mDCs) than in healthy controls at baseline. Both univariate (Kaplan-Meier) and multivariate (Cox regression) analyses were conducted to determine which variables (age, sex, baseline EDSS, MS relapse rates 1 year and 2 years before initiating IFNbeta-1a, mDCs and plasmacytoid (pDCs) subsets, activated and regulatory CD4(+) T-cells (T(Reg))) were associated with clinical response to IFNbeta-1a. During 1 year of treatment, we observed a shift towards lower proportions of CD123(+) pDCs expression and higher numbers and function of the T(Reg). Univariate analysis disclosed that MS activity was significantly associated with baseline BDCA1(+) mDCs below < or = 0.4% (p<0.0025). Cox model analysis revealed that baseline BDCA1(+) mDCs was the most closely associated factor with MS activity on IFN treatment during the 1-year follow-up (p<0.01). A better understanding of the rules that govern the T(Reg)-DC relationship will enable scientists to better manage the immune response in MS patients.

Circulating dendritic cells subsets and regulatory T-cells at multiple sclerosis relapse: differential short-term changes on corticosteroids therapy.

Glucocorticoids remain the treatment of choice for MS relapses. However, little is known on the effect of intravenous methylprednisolone (IVMP) on dendritic cells (DCs) and regulatory T-cells (TReg). Our main goal was to quantify circulating myeloid and plasmacytoid DCs (mDCs and pDCs), and TReg at MS relapse versus healthy controls; and to analyse the short-term changes after IVMP for MS relapse. MS patients at relapse compared to controls showed higher %CD4+CD25high+ TReg (p<0.01). After 5-days of IVMP, activated T-lymphocytes (p=0.001), pDCs (p<0.0001), and CD11c+ mDCs (p<0.0001) decreased. By contrast, CD4+CD25+ and CD4+CD25high+ TReg further increased (p<0.0001 both). Changes on these subsets may play a relevant role in the immunosuppressive activity of this drug.