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Effect of combined IFNb-1a and glatiramer acetate therapy on GA-specific T-cell responses in multiple sclerosis

Department of Neurology, University of Maryland and the Baltimore VA Medical Centre, Baltimore, Maryland, USA, sjalbut{at}umaryland.edu

M Chen

Department of Neurology, University of Maryland and the Baltimore VA Medical Centre, Baltimore, Maryland, USA

K Henschel

Department of Neurology, University of Maryland and the Baltimore VA Medical Centre, Baltimore, Maryland, USA

D Ford

Department of Neurology, University of Maryland and the Baltimore VA Medical Centre, Baltimore, Maryland, USA

K Costello

Department of Neurology, University of Maryland and the Baltimore VA Medical Centre, Baltimore, Maryland, USA

H Panitch

Department of Neurology, University of Maryland and the Baltimore VA Medical Centre, Baltimore, Maryland, USA

The combined treatment with interferon (IFN) and glatiramer acetate (GA) is of current interest in multiple sclerosis (MS). The therapeutic effect of GA in MS is believed to be mediated by GA-specific Th2 cells. IFN has a significant anti-proliferative effect on GA-induced lymphoproliferation in vitro. Therefore, we examined the possibility that IFN may interfere with the generation and phenotype of GA T-cell responses in MS patients receiving combined therapy. Sixty-six GA-specific T-cell lines (TCL) were generated ex vivo from five MS patients enrolled in an open-label clinical trial of combined IFN/GA treatment. Controls included 83 pretreatment and 131 on-treatment GA-TCL from 11 MS patients treated with GA only, and five GA-TCL generated from four patients receiving IFN -1a monotherapy. IFNg and IL-5 (markers of Th1 and Th2 responses, respectively) were assayed by ELISA in GA-TCL supernatants. Th1/Th2 bias was defined by the IFNg/IL-5 level ratio (> 2=Th1 bias, <0.5=Th2 bias, and 0.5- 2=Th0 bias). The frequency with which GA-reactive TCL were generated was 37.0% for the patients in the combination trial compared to 33.3% in the patients receiving GA alone. The mean stimulation index of the GA-TCL was 8.41 (range 2-42) for the combination compared to a mean of 6.29 (range 2-37) for the GA-treated group - a nonsignificant difference. Mean GA-TCL IFNg production was significantly lower in all treatment groups compared to pretreatment. IL-5 levels were enhanced in all treatment groups compared to pretreatment levels, but the change was not statistically significant. The Th1/Th0/Th2 distribution of GA-TCL was 7%/30%/63% for the GA+IFN group, 8%/9%/83% for the GA group, compared to 48%/21%/31% pre-GA treatment. All five GA-TCL from the IFN -1a monotherapy patients were Th2-biased. We conclude that IFN -1a does not affect the generation of GA-reactive T cells in vivo. Although more Th0 GA-TCL occurred with combination therapy than with GA treatment alone, both groups shared an overall Th2 bias. Therefore, we speculate that combined therapy is unlikely to reduce the efficacy of GA treatment in MS.

Key Words: Copaxone® • glatiramer acetate • interferon ß-1a • multiple sclerosis

Multiple Sclerosis, Vol. 8, No. 6, 485-491 (2002)
DOI: 10.1191/1352458502ms862oa


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