Hyaluronate receptor (CD44) and integrin alpha 4 (CD49d) are up-regulated on T cells during MS relapses

Department of Neurology, Kiinamyllynkatu 4-8, PL 52, FIN-20521, Turku, Finland.
Journal of Neuroimmunology (Impact Factor: 2.79). 10/2005; 166(1-2):189-92. DOI: 10.1016/j.jneuroim.2005.05.008
Source: PubMed

ABSTRACT A longitudinal study of peripheral blood T cell adhesion molecule expression was performed in 24 relapsing-remitting MS patients. There were 15 relapses in 11 patients during 15 months of observation. In comparison with remission, expression of hyaluronate receptor (CD44) was highly significant, and expression of integrin alpha4 (CD49d, VLA-4) significantly up-regulated during relapses. CD44 and CD49d are putative activity markers and CD44 a potential novel therapeutic target in MS.

1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: Natalizumab, a humanized monoclonal antibody against alpha4beta1 integrin, was shown in clinical trials to dramatically reduce the relapse rate, development of new magnetic resonance imaging (MRI) lesions and progression of disability in patients with relapsing multiple sclerosis. Following its expedited approval, sales of the drug were discontinued owing to the emergence of two cases of progressive multifocal leukoencephalopathy (PML), a rare but deadly viral infection of the central nervous system (CNS) associated with immunosuppression. Owing to the effect of natalizumab on central nervous system leukocyte recruitment, the emergence of PML has been attributed to diminished immunosurveillance. The lack of additional opportunistic or CNS infections among natalizumab-treated patients, however, suggests that alternate mechanisms may contribute to the infectious risk. This review examines how the inhibition of alpha4beta1-mediated adhesion might establish a unique milieu for the development of PML and how future approaches to selective adhesion molecule therapy in multiple sclerosis might avoid a similar fate.
    Neurological Research 05/2006; 28(3):291-8. DOI:10.1179/016164106X98189 · 1.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: CD4+ CD25(high) regulatory T cells (Tregs) of patients with relapsing-remitting (RR) multiple sclerosis (MS), in contrast to those of patients with secondary progressive (SP) MS, show a reduced suppressive function. In this study, we analysed forkhead box P3 (FOXP3) at the single-cell level in MS patients and controls (healthy individuals and patients with other neurological diseases) by means of intracellular flow cytometry. Our data revealed a reduced number of peripheral blood CD4+ CD25(high) FOXP3+ T cells and lower FOXP3 protein expression per cell in RR-MS patients than in SP-MS patients and control individuals, which was correlated with the suppressive capacity of Tregs in these patients. Interestingly, interferon (IFN)-beta-treated RR-MS patients showed restored numbers of FOXP3+ Tregs. Furthermore, a higher percentage of CD4+ CD25(high) FOXP3+ Tregs in RR-MS patients, as compared with controls and SP-MS patients, expressed CD103 and CD49d, adhesion molecules involved in T-cell recruitment towards inflamed tissues. This was consistent with a significantly increased number of CD27+ CD25(high) CD4+ T cells in the cerebrospinal fluid (CSF), as compared with peripheral blood, in RR-MS patients. Taken together, these data show aberrant FOXP3 expression at the single-cell level correlated with Treg dysfunction in RR-MS patients. Our results also suggest that Tregs accumulate in the CSF of RR-MS patients, in an attempt to down-regulate local inflammation in the central nervous system.
    Immunology 02/2008; 123(1):79-89. DOI:10.1111/j.1365-2567.2007.02690.x · 3.74 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It has long been thought that astrocytes, like other glial cells, simply provide a support mechanism for neuronal function in the healthy and inflamed central nervous system (CNS). However, recent evidence suggests that astrocytes play an active and dual role in CNS inflammatory diseases such as multiple sclerosis (MS). Astrocytes not only have the ability to enhance immune responses and inhibit myelin repair, but they can also be protective and limit CNS inflammation while supporting oligodendrocyte and axonal regeneration. The particular impact of these cells on the pathogenesis and repair of an inflammatory demyelinating process is dependent upon a number of factors, including the stage of the disease, the type and microenvironment of the lesion, and the interactions with other cell types and factors that influence their activation. In this review, we summarize recent data supporting the idea that astrocytes play a complex role in the regulation of CNS autoimmunity.
    Cellular and Molecular Life Sciences CMLS 07/2008; 65(17):2702-20. DOI:10.1007/s00018-008-8059-5 · 5.86 Impact Factor