Immunology 104 (4), 383-391
BenoîT Fellay, Michel Chofflon,
Catherine Juillard, Anne-Marie Paunier, Theodor Landis, Serge Roth and
Marie-Lise Gougeon
Summary
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-g
(IFN-g) and tumour
necrosis factor-a
(TNF-a) 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-a 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-g
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.
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