Intracellular cytokine profile in T-cell subsets of multiple sclerosis patients: different features in primary progressive disease.
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 hove 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 MS patients express significantly more CD4+ and CD8+ T cells were analyzed for IFN-gamma, IL-2, TNF-alpha, IL-4, IL-10 and IL-13 production.


RESULTS
cells producing IFN-gamma 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-alpha 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.
Killestein
J
J
Department of Neurology, VU Medical Center, Amsterdam, The Netherlands.
Den Drijver
B F
BF
Van der Graaff
W L
WL
Uitdehaag
B M
BM
Polman
C H
CH
Van Lier
R A
RA
D000328:Adult; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D016207:Cytokines / Q000032:analysis*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D018793:Interleukin-13 / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis* / Q000276:immunology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015415:Biomarkers; D016207:Cytokines; D018793:Interleukin-13; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma