Age-Associated T-Lymphocyte Activation through Mitogens in Patients with Multiple Sclerosis and Blood Donors

Prolonged clinico-immunological observation of 85 patients with definite multiple sclerosis (MS) was performed in order to elucidate the connections between the clinical and immune state. A battery of immunological investigations was performed, including estimation of T-cell subpopulations in blood and cerebrospinal fluid (CSF); proliferative responses of circulating lymphocytes to mitogens, recombinant interleukin-2 (rIL2) and myelin basic protein levels in different culture conditions; levels of immunoglobulin (Ig) in sera and CSF, and of Ig production in vitro; indices of IL2 synthesis and IL2 sensitivity; production of prostaglandin E2 and tumour necrosis factor (TNF) alpha by monocytes and levels of beta-endorphin in sera and supernatants phytohaemagglutinin of (PHA)-activated cells. Clinical observation was performed periodically using Kurtzke scales and was supplemented by repeated recording of evoked potentials and magnetic resonance imaging. Initial investigations showed specific differences between patients with MS and the control groups (donors and patients with other neurological disorders of the same age). Correlative and regressive analyses showed no association between immunological and clinical parameters at the initial investigation, although immunological indexes were inter-related, and indicated specific alterations in immunoregulation in MS. Retrospective analysis revealed associations between the clinical status of patients with MS and their previous immune status. Evidence of cell activation--including a decreased percentage of circulating cells with differential antigens, lower cell mitogen-induced proliferative responses in vitro, with restoration following the addition of autoserum, greater IL2 sensitivity, and increased TNF-alpha production by macrophages--often predicted the clinical manifestation of deterioration. It is proposed that the immunopathological process in MS has a number of stages with characteristic features, and that progression from one stage to another can be subclinical. No single immunological index can be used to determine stage. Only systemic alterations reflect the real situation, whilst every patient has some abnormalities. A system of clinico-immunological monitoring could severe as the basis for a new approach to the dynamic treatment of MS.

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Prolonged dynamic clinico-immunological observation of 85 patients with definite multiple sclerosis: First steps towards monitoring process activity

Гусев

Demina

Бойко

et al. 1994

J Neurol

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Increased Spontaneous Ex Vivo Apoptosis and Subset Alterations in Peripheral Blood T Cells from Patients with Multiple Sclerosis

et al. 2006

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In order to characterize the immunophenotype and the lymphocyte apoptosis in multiple sclerosis (MS) patients, the peripheral blood lymphocytes of 46 MS patients and 12 healthy volunteers were studied by flow cytometry. Immunophenotypic alterations included significant increases in T CD4+ lymphocytes and reductions in the percentages of CD3+ and CD8+ T cells. After 24 h of culture spontaneous apoptosis was increased in almost T lymphocyte subsets from MS patients and it was significantly higher in those patients who had suffered more than two relapses in the two previous years. The incidence of spontaneous apoptosis was not dependent on FasL-Fas interactions and correlated with the percentages of cells positive for active caspases but not with percentages of Fas+ cells. The increased susceptibility to apoptosis of peripheral blood T lymphocytes from MS patients is difficult to reconcile with the previously proposed role of a defective lymphocyte apoptosis in the pathophysiology of MS.

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IFNβ therapy progressively normalizes the increased ex vivo T lymphocyte apoptosis observed in active patients with multiple sclerosis

García‐Merino

Barcenilla

Díaz

et al. 2009

Clinical Immunology

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Age-Associated T-Lymphocyte Activation through Mitogens in Patients with Multiple Sclerosis and Blood Donors

Cited by 5 publications

References 9 publications

Prolonged dynamic clinico-immunological observation of 85 patients with definite multiple sclerosis: First steps towards monitoring process activity

Prolonged dynamic clinico-immunological observation of 85 patients with definite multiple sclerosis: First steps towards monitoring process activity

Increased Spontaneous Ex Vivo Apoptosis and Subset Alterations in Peripheral Blood T Cells from Patients with Multiple Sclerosis

IFNβ therapy progressively normalizes the increased ex vivo T lymphocyte apoptosis observed in active patients with multiple sclerosis

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