The median percentages of peripheral blood immunoglobulin-positive (Ig+) lymphocytes (8%, n = 46), CD8+ (12%, n = 49) and CD57+ cell numbers (5%, n = 37) of patients suffering from multiple sclerosis (MS) were significantly (p < 0.05) lower than the values of age- and sex-matched healthy individuals (Ig+ cells: 13%, n = 46; CD8+ cells: 17%, n = 49; CD57+ cells: 9%, n = 37). Comparison of calculations on decreased peripheral blood cell counts and increased brain cell counts in MS patients revealed that sequestration of blood cells into the MS brain is a possible explanation of these findings.
Immune system suppression after cardiac surgery is reflected in prolonged diminished HLA-DR expression on monocytes and B-lymphocytes. Suppression is not irreversible but can - at least IN VITRO - be overridden by the immunostimulating compound GM-CSF.
Background: The pathophysiology of multiple sclerosis (MS)-associated fatigue is poorly understood. Immunological mechanisms may play a role. Alterations in immunological profile indicate a chronic immune activation in MS patients with fatigue. T-regulatory (Treg) cells seem to play a key role in coordinating autoimmune mechanisms in MS. This is the first study investigating the relationship between Treg cell function and fatigue in MS patients. Methods: In this cross-sectional in vitro, ex vivo study, we isolated peripheral blood mononuclear cells (PBMCs) from 20 MS patients with fatigue, determined lymphocyte subsets by flow cytometry and suppressive function of Treg cells in PBMC cultures with antigen stimulation. Forkhead box protein 3 expression was evaluated by PCR. Results were compared with 20 MS patients without fatigue and with 19 healthy controls. Results: Leukocytes and lymphocyte subsets including Treg cell frequency did not differ in patients with and without fatigue. Co-culturing of Treg cells with CD4+CD25– cells did not lead to a significant suppression of myelin basic protein- and pokeweed mitogen-induced proliferation in MS patients in contrast to healthy controls. There were no statistical differences between MS patients with and without fatigue regarding this suppression activity. Conclusions: Fatigue seems not to be associated with impaired function of Treg cells in untreated MS patients.
In 128 patients with multiple sclerosis (MS) and 204 blood donors (control persons) the in vitro activation of ‘Ficoll-purified’ peripheral blood T lymphocytes was measured using the 3H-thymidine incorporation rate without (spontaneous proliferation) and with mitogen addition (concanavalin A, phytohemagglutinin). Mitogen responsiveness in control persons and MS patients decreased with age, reflecting a T-lymphocyte inherent mechanism for the diminution of responsiveness. The MS patients, ranging in age between 20 and 30 years, showed decreased mitogen responsiveness and a tendency to increased spontaneous proliferation compared to the control persons. These results could be an expression of a viral infection.
Background: Metastatic renal cancer is considered not to benefit from treatment by present-day methods. Clinical and experimental experience lead to the suggestion that mechanisms exerted by the immune system favour the outcome of patients with metastatic renal carcinoma. Immunomodulating therapy with interferon-gamma has been proved to be clinically effective in etastatic renal carcinoma. Material and Methods: A non-randomized phase-II study was initiated to observe the clinical and immunological effects of 200 μg interferon-gamma (IFN-gamma) s. c. once weekly in patients with metastatic renal carcinoma. Twenty patients were enrolled in this study. The protocol was accepted by the Ethical Committee of the Medical Faculty, University of Essen. Clinical data, cellular and humoral immune system parameters were monitored over 6 months. Results: Median survival of the patients was 12 months. No complete or partial remission could be documented. We observed a significant increase in lymphocyte, B, T, T helper and natural killer (NK) cell counts after 6 months of treatment compared to the appropriate pretreatment values. Concentrations of complement C3, C4 and immunoglobulins (Ig) A, IgG and IgM were also significantly increased after treatment with IFN-gamma. Pretreatment values of B, T, T helper and NK cells were decreased and complement serum values were increased in comparison to normal values. Conclusion: Although a significant increase of the investigated immunologie parameters after IFN-gamma therapy could be seen, no clinical remission was associated with this treatment modality. The validity and usefulness of immunomonitoring in metastatic renal cancer has to be discussed again.
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