Interferon‐β therapy reduces CD4⁺ and CD8⁺ T‐cell reactivity in multiple sclerosis

Abstract

Summary Therapy with interferon‐β (IFN‐β) has well‐established clinical effects in multiple sclerosis (MS), albeit the immunomodulatory mechanisms are not fully understood. We assessed the prevalence and functional capacity of CD4+ and CD8+ T cells in healthy donors, and in untreated and IFN‐β‐treated MS patients, in response to myelin oligodendrocyte glycoprotein (MOG). The proportion of CD45RO+ memory T cells was higher in MS patients than in healthy donors, but returned to normal values upon therapy with IFN‐β. While CD45RO+ CD4+ T cells from all three groups responded to MOG in vitro, untreated patients showed augmented proliferative responses compared to healthy individuals and IFN‐β treatment reduced this elevated reactivity back to the values observed in healthy donors. Similarly, the response of CD45RO+ CD8+ T cells to MOG was strongest in untreated patients and decreased to normal values upon immunotherapy. Overall, the frequency of peripheral CD45RO+ memory T cells ex vivo correlated with the strength of the cellular in vitro response to MOG in untreated patients but not in healthy donors or IFN‐β‐treated patients. Compared with healthy individuals, responding CD4+ and CD8+ cells were skewed towards a type 1 cytokine phenotype in untreated patients, but towards a type 2 phenotype under IFN‐β therapy. Our data suggest that the beneficial effect of IFN‐β in MS might be the result of the suppression or depletion of autoreactive, pro‐inflammatory memory T cells in the periphery. Assessment of T‐cell subsets and their reactivity to MOG may represent an important diagnostic tool for monitoring successful immunotherapy in MS.

PGE2 Contributes to In vitro MSC‐Mediated Inhibition of Non‐Specific and Antigen‐Specific T Cell Proliferation in MS Patients

“…, Table ) that corresponds to the results of other authors . rMOG was used as in vitro potential target autoantigen and as the most immunogenic and acceptable protein for assessing the intensity of cellular and humoral reactions in MS according to our previous data . According to this study, inhibitory effects of allogeneic as well as autologous MSC from patients with MS on myelin‐specific T cell proliferation were more expressed as compared to the analysed data in healthy donors (Fig.…”

IFN-β differentially regulates the function of T cell subsets in MS and EAE

“…Treatment of MS patients with IFN-β is shown to reduce the frequency of VLA4 + CD8 + T cells among total PBMCs, as well as VLA4 surface expression [44]. Similar results were obtained upon MOG stimulation of PBMCs from IFN-β-treated MS patients, where decreased frequencies of CD8 + and CD8 + IFN-γ + T cells were observed [91].…”

Anti-CD20 therapy depletes activated myelin-specific CD8+T cells in multiple sclerosis

“…CD8 + T cells specific for myelin antigens are also pathogenic in various EAE models (19)(20)(21)(22)(23). Prior efforts to study myelinspecific CD8 + T cells have been hampered by technical limitations and reliance on in vitro manipulation (24)(25)(26)(27)(28)(29)(30). In this study, we employed pMHC I tetramer-based methods to unambiguously identify myelin-specific CD8 + T cell populations directly from the peripheral blood without in vitro stimulation or manipulation.…”

“…Myelin is considered a putative target autoantigen in MS (18), and myelin-specific CD8 + T cells are well known to contribute to CNS pathology in experimental autoimmune encephalomyelitis (EAE) (19)(20)(21)(22)(23). A number of studies have described the reactivity of human CD8 + T cells against myelin antigens (24)(25)(26)(27)(28)(29)(30); however, reports are conflicting whether myelin-specific CD8 + T cell responses differ between MS patients and controls (24,(27)(28)(29)(30). Much of the prior work was limited by a reliance on functional assays, precluding the sensitive detection of unmanipulated epitopespecific CD8 + T cell populations.…”