T cell response to myelin basic protein before and after treatment with interferon beta in multiple sclerosis

Ristori, Giovanni; Montesperelli, C.; Gasperini, Claudio; Battistini, Luca; Borsellino, Giovanna; Buttinelli, Carla; Cannoni, Stefania; Perna, Alessia; Pozzilli, Carlo; Salvetti, Marco

doi:10.1016/s0165-5728(99)00107-1

Cited by 13 publications

(3 citation statements)

References 32 publications

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“…Since its first use, several hundred studies have examined the mechanisms of IFN‐β treatment in MS. The most important mechanisms of action for IFN‐β, which have been shown to include stabilization of the blood–brain barrier (BBB) by blocking matrix metalloproteases in in vitro models and in treated MS patients , the downregulation of HLA class II molecules and antigen presentation on glial cells and B cells in vitro , and the inhibition of proinflammatory and upregulation of Th2 cytokines by T cells of IFN‐β‐treated patients , although some of these observations remain controversial . Whether IFN‐β antiviral activity also contributes to the clinical effects is not clear, but more than 20 years of clinical use have shown that IFN‐β treatment does not lead to any compromise of the immune system with respect to protection against viral, bacterial, or fungal infections.…”

Section: Treatments Of Msmentioning

confidence: 99%

Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis

et al. 2016

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Multiple sclerosis (MS) is the most common inflammatory disorder of the central nervous system (CNS) in young adults. When MS is not treated, it leads to irreversible and severe disability. The etiology of MS and its pathogenesis are not fully understood. The recent discovery that MS-associated genetic variants code for molecules related to the function of specific immune cell subsets is consistent with the concept of MS as a prototypic, Tcell-mediated autoimmune disease targeting the CNS. While the therapeutic efficacy of the currently available immunomodulatory therapies further strengthen this concept, differences observed in responses to MS treatment as well as additional clinical and imagingobservations have also shown that the autoimmune pathogenesis underlying MS is much more complex than previously thought. There is therefore an unmet need for continued detailed phenotypic and functional analysis of disease-relevant adaptive immune cells and tissues directly derived from MS patients to unravel the immune etiology of MS in its entire complexity. In this review, we will discuss the currently available MS treatment options and approved drugs, including how they have contributed to the understanding of the immune pathology of this autoimmune disease.Keywords: Autoantibodies r Autoimmune pathogenesis r Autoimmunity r Autoreactive B cells r Autoreactive T cells r Experimental autoimmune encephalomyelitis r Multiple sclerosis r Treatment Introduction-MS as an autoimmune diseaseMS is considered a prototypic organ-specific autoimmune disease targeting the CNS with inflammatory lesions, demyelination, axonal/neuronal damage, and metabolic changes [1,2]. Relapsing-remitting and secondary progressive MS (RRMS, SPMS) are the two most frequent forms of MS, which often affect young adults between 20 and 40 years of age, and women three times more often than men [3]. Typical clinical signs include temporary loss of vision, sensory and motor problems, but also fatigue, neurocognitive changes, and impairment of bladder, bowel, and Correspondence: Britta Engelhardt ; Roland Martin e-mail: bengel@tki.unibe.ch; roland.martin@usz.ch sexual functions. During the relapsing-remitting phase neurological deficits, which occur in bouts and may last from days to a few weeks, usually disappear again, but after several years, disability gradually builds up. Depending on the individual course this secondary progressive disease with continuously increasing disability may never set in, but often starts after 15-20 years of RRMS. In a small percentage of patients such a progressive course is seen from the beginning, which is referred to as primary progressive MS (PPMS) and seen in females and males with equal frequency [3].Evidence for an autoimmune pathogenesis of MS was shown in its animal model, experimental autoimmune encephalomyelitis (EAE) (summarized in [4,5] Treatments of MSAs already noted above, the various treatments of MS deserve particular mentioning not only because they have changed clinical practice and can be considered ...

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Section: Treatments Of Msmentioning

confidence: 99%

Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis

et al. 2016

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“…In experimental studies focused on the IFN-β mechanism of action, the antiproliferative activity, modulation of leukocytes adhesion molecules, inhibition of matrix metalloproteinases activity, alteration of leukocytes trafficking, all affect immune function features, for example modulation of NK cells activity [33], antagonism towards pro-inflammatory cytokines and induction of immunosuppressive cytokines [27] have been established. Many unanswered questions, however, still remain about INF-β.…”

Section: Introductionmentioning

confidence: 99%

Changes of percentages in immune cells phenotypes and cytokines production during two-year IFN-?-1a treatment in multiple sclerosis patients

Mirowska

Skierski

Paź

et al. 2003

Journal of Neurology

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“…IFN-ß can influence the outcome of immune cell activation by modifying the response of antigen-presenting cells and T cells to accessory molecule signals. The most relevant immunomodulatory effects of IFN-ß-la are the inhibition of the proliferation of autoreactive T cells, the inhibition of the expression of MHC class II molecules, antagonism toward pro-inflammatory cytokines, and the induction of immunosuppressive ones [10]. But many questions about IFN-ß-la are as yet unanswered.…”

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Changes in the Immunological Profile of Peripheral Blood Leukocytes in Multiple Sclerosis (MS) Patients Treated with lnterferon-ß-1 a. Veränderungen des immunologischen Profils von Leukozyten im peripheren Blut von Multiple-Sklerose-(MS-)Patienten, behandelt mit lnterferon-ß-1 a

Mirowska¹,

Paź²,

Zaborski³

et al. 2001

LaboratoriumsMedizin

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Interferon (IFN-ß) has beneficial effects in multiple sclerosis (MS) probably by regulating the immune system. The aim of this study was to find out whether IFN-ß-la influences the immune profile of peripheral blood (PB) leukocytes in MS patients. We studied 21 outpatients (12 women and nine men; mean age: 37.2 years) with relapsing-remitting MS who had been treated with IFN-ß-la (30 fig i.m. once a week) for 9 months. Phenotype analysis of PB leukocytes was carried out using two-color flow cytometry. The following antigens were determined: CD3, CD4, CDS, CD14, CD19, CD56, CD16, CD25, CD38, CD80, CD86. Blood samples were collected before IFN-ß-la administration as well as after 3, 6, and 9 months of treatment. We found a statistically significant decrease of CD19 + cells (B lymphocytes) after 3 months of IFN-ß-l.a administration. After 6 and 9 months of IFN-ß-la therapy, the percentage of CD14+CD86+ cells (monocytes with expression of costimulatory molecules) and CD3+CD25+ cells (activated T cells) increased. The percentage of CD56 + CD16 + cells (NK cells) decreased after 3, 6, and 9 months. CD14+CD86+ cells are involved in Th2 lymphocyte activation, which releases anti-inflammatory cytokines. This possibly limits myelin sheath damage resulting from inflammation. CD3 + CD25 + cells may also represent Th2 cell populations. B lymphocytes (CD19 + cells) may be responsible for the production of immunoglobulins directed against myelin components, so . Eingegangen: 28. Dezember 2000/Angehommen: 5. März 2001 that the decrease in their percentage might be due to the suspected positive action of IFN-ß-la in MS patients. Our results indicate that IFN-ß-la affects immunocompetent cell populations in MS, which may influence the clinical course of the disease.

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T cell response to myelin basic protein before and after treatment with interferon beta in multiple sclerosis

Cited by 13 publications

References 32 publications

Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis

Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis

Changes of percentages in immune cells phenotypes and cytokines production during two-year IFN-?-1a treatment in multiple sclerosis patients

Changes in the Immunological Profile of Peripheral Blood Leukocytes in Multiple Sclerosis (MS) Patients Treated with lnterferon-ß-1 a. Veränderungen des immunologischen Profils von Leukozyten im peripheren Blut von Multiple-Sklerose-(MS-)Patienten, behandelt mit lnterferon-ß-1 a

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