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Intracellular cytokine profile in T-cell subsets of multiple sclerosis patients: different features in primary progressive disease

Department of Neurology, VU Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands, Department of Clinical Viro-Immunology, CLB, PO Box 9092, 1066 CX, Amsterdam, The Netherlands

B F Den Drijver

Department of Neurology, VU Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands

W L Van der Graaff

Department of Neurology, VU Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands

B MJ Uitdehaag

Department of Neurology, VU Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands

C H Polman

Department of Neurology, VU Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands

R AW Van Lier

Department of Clinical Viro-Immunology, CLB, PO Box 9092, 1066 CX, Amsterdam, The Netherlands

Objective: To evaluate the expression of cytokines in both CD4⁺ and CD8⁺ T cells derived from peripheral blood of untreated multiple sclerosis (MS) patients with either relapsing-remitting (RR), secondary progressive (SP) or primary progressive (PP) MS and healthy controls (HC). Background: MS is an immune-mediated disease and cytokines have been hypothesized to contribute significantly to disease progression. Compared to the relapse-onset (RR, SP) form of the disease, PPMS patients have different clinical, immunological and pathological features. Surprisingly, the ability of their circulating T cells to produce immunoregulatory cytokines has not been extensively studied so far. Methods: Seventy-two MS patients (24 RR, 26 SP, 22 PP) and 34 HC were studied. Stimulated peripheral blood derived CD4⁺ and CD8⁺ T cells were analyzed for IFN-g, IL-2, TNF-a, IL-4, IL-10 and IL-13 production. Results: MS patients express significantly more CD4⁺ and CD8⁺ T cells producing IFN-g compared to HC. Compared to the other forms of the disease, PPMS patients display a significant decrease in CD4⁺ T cells producing IL-2, IL-13 and TNF-a and a significant increase in CD8⁺ T cells producing IL-4 and IL-10. Conclusions: The data presented here demonstrate that patients with PPMS express less pro- and more anti-inflammatory cytokine producing T cells compared to the relapse-onset form of the disease, confirming the view on PPMS as a distinct disease entity.

Key Words: T cells • cytokines • primary progressive MS

Multiple Sclerosis, Vol. 7, No. 3, 145-150 (2001)
DOI: 10.1177/135245850100700302


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