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

2001 ◽  
Vol 7 (3) ◽  
pp. 145-150 ◽  
Author(s):  
J. Killestein ◽  
B.F. den Drijver ◽  
W.L. van der Graaff ◽  
B.M.J. Uitdehaag ◽  
C.H. Polman ◽  
...  
2011 ◽  
Vol 18 (6) ◽  
pp. 788-798 ◽  
Author(s):  
M Chiarini ◽  
F Serana ◽  
C Zanotti ◽  
R Capra ◽  
S Rasia ◽  
...  

Background: Interferon-beta is used to reduce disease activity in multiple sclerosis, but its action is incompletely understood, individual treatment response varies among patients, and biological markers predicting clinical benefits have yet to be identified. Since it is known that multiple sclerosis patients have a deficit of the regulatory T-cell subsets, we investigated whether interferon-beta therapy induced modifications of the two main categories of regulatory T cells (Tregs), natural and IL-10-secreting inducible Tr1 subset, in patients who are biologically responsive to the therapy. Methods: T-cell phenotype was determined by flow cytometry, while real-time PCR was used to evaluate interferon-beta bioactivity through MxA determination, and to measure the RNA for IL-10 and CD46 molecule in peripheral blood mononuclear cells stimulated with anti-CD46 and anti-CD3 monoclonal antibodies, which are known to expand a Tr1-like population. Results: Interferon-beta induced a redistribution of natural Treg subsets with a shift of naive Tregs towards the ‘central memory-like’ Treg population that expresses the CCR7 molecule required for the in vivo suppressive activity. Furthermore, in a subgroup of treated patients, the CD46/CD3 co-stimulation, probably through the Tr1-like subset modulation, increased the production of RNA for IL-10 and CD46. The same group showed a lower median EDSS score after two years of therapy. Conclusions: The selective increase of ‘central memory-like’ subset and the involvement of the Tr1-like population may be two of the mechanisms by which interferon-beta achieves its beneficial effects. The quantification of RNA for IL-10 and CD46 could be used to identify patients with a different response to interferon-beta therapy.


2001 ◽  
Vol 7 (3) ◽  
pp. 145-150 ◽  
Author(s):  
J Killestein ◽  
B F Den Drijver ◽  
W L Van der Graaff ◽  
B MJ Uitdehaag ◽  
C H Polman ◽  
...  

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.


PLoS ONE ◽  
2016 ◽  
Vol 11 (7) ◽  
pp. e0159565 ◽  
Author(s):  
Zahra Salehi ◽  
Rozita Doosti ◽  
Masoumeh Beheshti ◽  
Ehsan Janzamin ◽  
Mohammad Ali Sahraian ◽  
...  

1998 ◽  
Vol 4 (3) ◽  
pp. 174-177 ◽  
Author(s):  
A M Ferrarini ◽  
S Sivieri ◽  
M Buttarello ◽  
A Facchinetti ◽  
P Perini ◽  
...  

To identify immunological markers that could be used to monitor relapsing-remitting multiple sclerosis (RRMS) course/activity during interferon beta 1b (IFNβ1b) therapy, we longitudinally studied HLA-DR and CD25 expression by T lymphocytes in 15 IFNβ1b-treated RRMS patients. Peripheral blood T cell subsets were analysed before therapy (T0), and after 1 (T1), 2 (T2), 3 (T3), 6 (T4) and 12 (T5) months after therapy initiation. HLADR expression and the CD3+HLA-DR+ T cell number showed a peculiar trend in almost all (14/15) the patients: a significant decrease at T1 and T2 followed by a return to pre-treatment levels from T3 to T5. At T1 and T2, eight patients showed an up-regulation of CD25 on CD4, as well as an increase in the CD4+CD25+ cell number. However, a marked, significant reduction of this T cell subset was observed in all the patients at T3, followed by the progressive return to pre-treatment values from T4 to T5. All the patients developed anti-IFNβ1b `binding' antibodies within the first three months of therapy. Our findings demonstrate that: (1) the expression of HLA-DR and CD25 on T cells, as well as the number of circulating CD3+HLA-DR+ and CD4+CD25+ cells, are only transiently reduced in vivo in IFNβ1b-treated RRMS patients, (2) the expression of HLA-DR and CD25 on T lymphocytes cannot be used to monitor MS course/activity during IFNβ1b therapy, (3) the long-lasting beneficial effect of IFNβ1b on RRMS reported in the literature cannot be explained by the down-regulation of MHC class II antigens and/or interleukin-2 receptor expression induced by this cytokine.


2018 ◽  
Vol 48 (8) ◽  
pp. 1376-1388 ◽  
Author(s):  
Priscila M. Sacramento ◽  
Clarice Monteiro ◽  
Aleida S. O. Dias ◽  
Taissa M. Kasahara ◽  
Thaís B. Ferreira ◽  
...  

2013 ◽  
Vol 20 (7) ◽  
pp. 790-801 ◽  
Author(s):  
Kim Pannemans ◽  
Bieke Broux ◽  
An Goris ◽  
Bénédicte Dubois ◽  
Tom Broekmans ◽  
...  

Background: The importance of Qa-1 restricted CD8+ T cells in regulating autoreactive T cell responses has been demonstrated in animal models for autoimmune disorders, including multiple sclerosis (MS). Objective: We hypothesize that their human variant, HLA-E restricted CD8+ T cells, fulfills a similar regulatory role in man and that these cells are of importance in MS. Methods: A large cohort of MS patients and healthy controls was genotyped for the two known HLA-E polymorphisms. Flow cytometry was used to determine HLA-E expression kinetics and to phenotype HLA-E restricted CD8+ T cells. Immunohistochemistry was performed to investigate HLA-E expression in the central nervous system (CNS) of MS patients. Results: HLA-E is upregulated on immune cells upon in vitro activation and this upregulation is polymorphism-dependent for T and B cells. T and B cells in lesions of MS patients show enhanced HLA-E expression. Furthermore, NKG2C+CD8+ T cells of MS patients have a significantly lower Foxp3 expression, while NKG2A+CD8+ T cells of MS patients produce higher levels of pro-inflammatory cytokines compared to those of healthy individuals. Conclusion: Our study indicates that the HLA-E system is altered in MS and could play a regulatory role in disease.


Author(s):  
Fatma Betul Oktelik ◽  
Vuslat Yilmaz ◽  
Recai Turkoglu ◽  
Ece Akbayir ◽  
Erdem Tuzun ◽  
...  

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