sq-23377 and Multiple-Sclerosis

Patients with relapsing-remitting (RR) and secondary progressive (SP) forms of multiple sclerosis (MS), although in long-term clinical remission, showed different patterns of increased expressions of the activation markers: CD69, CD40L, and both membrane/surface and cytoplasmic CTLA-4 (mCTLA-4 and cCTLA-4, respectively) in freshly isolated peripheral blood (PB) CD4+ T cells compared with controls. Also observed were dysregulated responses to ex vivo stimulation in both groups of MS patients accompanied by increased IFN-gamma synthesis. Our findings may suggest that the mechanisms leading to each clinical form of the disease may be heterogeneous.

Topics: Adult; Antigens, CD; Antigens, Differentiation; Antigens, Differentiation, T-Lymphocyte; Antiviral Agents; CD4-Positive T-Lymphocytes; CD40 Ligand; Cells, Cultured; CTLA-4 Antigen; Female; Flow Cytometry; Gene Expression Regulation; Humans; Interferon-gamma; Ionomycin; Lectins, C-Type; Lymphocyte Activation; Male; Middle Aged; Multiple Sclerosis; Statistics, Nonparametric; Time Factors

To determine the frequency of in vivo activated T(H)1 lymphocytes, T-cell subsets of 9 multiple sclerosis patients with active disease and 17 healthy controls were analyzed by immunostaining for CCR5, CD26, and their expression of interleukin-2, interferon-gamma, and tumor necrosis factor-alpha. The numbers of CCR5+ interferon-gamma- and tumor necrosis factor-alpha-producing T cells were significantly increased in the peripheral blood of multiple sclerosis patients. CCR5 expression may be a useful marker to identify effector cells in multiple sclerosis and could be used as a tool for monitoring disease activity.

Topics: Adult; Dipeptidyl Peptidase 4; Female; Humans; Interferon-gamma; Ionomycin; Lymphocyte Count; Male; Middle Aged; Multiple Sclerosis; Receptors, CCR5; Reference Values; T-Lymphocytes; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha

In this study we have examined intracellular cytokines in peripheral blood mononuclear cells (PBMC) of MS patients by flow cytometry (cytokine flow cytometry). MS progressive patients showed an increased number of cells producing interferon-gamma (IFN-gamma) after activation with phorbol 12-myristate 13-acetate and ionomycin, compared with patients with clinically inactive forms (P < 0001) and with healthy controls (P = 0001). These cells belonged to the CD4+ and CD8+ subsets in similar proportions. Clinically inactive patients showed a lower level of cells producing IL-2 than controls (P = 0.03) and active MS patients (P = 0.03). Most IL-2-producing cells were CD4+ lymphocytes, although a small part of the IL-2 was also produced by CD8+ cells. The percentage of cells producing simultaneously IL-2 and IFN-gamma was increased in active MS and they were mainly CD4+ lymphocytes. No differences in the production of IL-4 were observed between groups. However, we found an increased IL-10 production in clinically active MS patients (P = 0.03). Treatment with IFN-beta of active MS patients showed lower levels of cytokines when compared with untreated MS patients. This methodological approach could help in the follow up and therapeutic monitoring of MS patients.

Topics: Adult; Aged; Case-Control Studies; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cytokines; Female; Flow Cytometry; Humans; In Vitro Techniques; Interferon-beta; Interferon-gamma; Interleukin-10; Interleukin-2; Ionomycin; Lymphocyte Activation; Male; Middle Aged; Multiple Sclerosis; Phenotype; Tetradecanoylphorbol Acetate

Activated T cells are able to stimulate proliferation in resting T cells through an antigen non-specific mechanism. The in vivo usefulness of this T cell-T cell activation is unclear, but it may serve to amplify immune responses. T cell-T cell activation could be involved in the well-documented occurrence of multiple sclerosis (MS) exacerbations following viral infections. Excessive activation via this pathway could also be a factor in the etiology of MS. We tested the hypothesis that excessive T cell-T cell activation occurs in MS patients using in vitro proliferation assays comparing T cells from MS patients to T cells from controls. When tested as responder cells, T cells from MS patients proliferated slightly less after stimulation with previously activated cells than T cells from controls. When tested as stimulator cells, activated cells from MS patients stimulated slightly more non-specific proliferation than activated cells from controls. Neither of these differences were statistically significant. We conclude that T cell proliferation in response to activated T cells is similar in MS and controls.

Topics: Antigens, CD; CD3 Complex; Cells, Cultured; Disease Progression; Humans; Ionomycin; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Multiple Sclerosis; Recurrence; Reference Values; T-Lymphocytes; Tetradecanoylphorbol Acetate