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Brigitte Wildemann

Publications and source records attributed to Brigitte Wildemann.

10 recordsLinked to original sources
PubMed2006

Similar sensitivity of regulatory T cells towards CD95L-mediated apoptosis in patients with multiple sclerosis and healthy individuals.

Impaired suppressive function of CD4(+)CD25(high) regulatory T cells (T(reg)) has been reported as a novel pathogenetic mechanism in Multiple sclerosis (MS). We addressed if high apoptosis sensitivity of MS-T(reg) could explain this functional T(reg) defect. T(reg) from treatment-naïve MS patients showed high sensitivity towards CD95Ligand-mediated apoptosis and exhibited enhanced cell death to IL-2 and TCR-signal deprivation. Since susceptibility of T(reg) to cell death was similar in MS patients and healthy controls, this cannot explain the inhibitory dysfunction of T(reg) associated with MS. Furthermore, as cell death is not enhanced, therapeutic expansion of MS-T(reg)in vitro should be a reasonable and novel therapeutic option.

Adult↗
PubMed2005

In contrast to effector T cells, CD4+CD25+FoxP3+ regulatory T cells are highly susceptible to CD95 ligand- but not to TCR-mediated cell death.

CD4(+)CD25(+)FoxP3(+) regulatory T cells (T(reg)) suppress T cell function and protect rodents from autoimmune disease. Regulation of T(reg) during an immune response is of major importance. Enhanced survival of T(reg) is beneficial in autoimmune disease, whereas increased depletion by apoptosis is advantageous in cancer. We show here that freshly isolated FACS-sorted T(reg) are highly sensitive toward CD95-mediated apoptosis, whereas other T cell populations are resistant to CD95-induced apoptosis shortly after isolation. In contrast, TCR restimulation of T(reg) in vitro revealed a reduced sensitivity toward activation-induced cell death compared with CD4(+)CD25(-) T cells. Thus, the apoptosis phenotype of T(reg) is unique in comparison to other T cells, and this might be further explored for novel therapeutic modulations of T(reg).

Apoptosis↗
PubMed2005

Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis.

Immunoregulatory T cells of (CD4+)CD25+ phenotype suppress T cell function and protect rodents from organ-specific autoimmune disease. The human counterpart of this subset of T cells expresses high levels of CD25 and its role in human autoimmune disorders is currently under intense investigation. In multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), the activation of circulating self-reactive T cells with specificity for myelin components is considered to be an important disease initiating event. Here, we investigated whether MS is associated with an altered ability of (CD4+)CD25high regulatory T cells (Treg) to confer suppression of myelin-specific immune responses. Whereas Treg frequencies were equally distributed in blood and cerebrospinal fluid of MS patients and did not differ compared to healthy controls, the suppressive potency of patient-derived (CD4+)CD25high T lymphocytes was impaired. Their inhibitory effect on antigen-specific T cell proliferation induced by human recombinant myelin oligodendrocyte protein as well as on immune responses elicited by polyclonal and allogeneic stimuli was significantly reduced compared to healthy individuals. The effect was persistent and not due to responder cell resistance or altered survival of Treg, suggesting that a defective immunoregulation of peripheral T cells mediated by (CD4+)CD25high T lymphocytes promotes CNS autoimmunity in MS.

Adolescent↗
PubMed2005

[Meningitis].

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Anti-Bacterial Agents↗
PubMed2004

Acute and long-term alteration of chemokine mRNA expression after anti-viral and anti-inflammatory treatment in herpes simplex virus encephalitis.

Mortality and morbidity rates remain high among patients with herpes simplex virus encephalitis (HSVE). Chemokine-mediated recruitment and activation of leukocytes to focal areas of viral CNS infection are crucial steps in antiviral response and clearance. However, the inflammatory reaction and cellular antiviral response may enhance collateral damage to neurons and account for chronic progressive brain damage. We identified a specific mRNA expression of the interferon-gamma-inducible chemokines (CXCL9, CXCL10 and CXCL11), and RANTES (CCL5) in the acute course and long-term of experimental HSVE. This pattern was substantially altered by anti-viral and anti-inflammatory treatment. Our findings indicate a pivotal role of these chemokines in the immunopathogenesis of HSVE.

Acyclovir↗
PubMed2004

Single-cell PCR analysis of the immunoglobulin heavy-chain CDR3 region for the diagnosis of leptomeningeal involvement of B-cell malignancies using standard cerebrospinal fluid cytospins.

The diagnosis of leptomeningeal B-cell malignancies is based on the identification of malignant B cells in the cerebrospinal fluid (CSF). We have established a polymerase chain reaction (PCR) approach to characterize the clonally diverse gene encoding the immunoglobulin heavy-chain (IgH) third complementarity determining region (CDR3) of single B cells. We demonstrate that single-cell PCR is readily applicable to individual cells derived from routine CSF cytospins and is a powerful method to discriminate monoclonal neoplastic from polyclonal reactive B-cell responses. Single-cell PCR analysis, as a new tool for the diagnosis and monitoring of neoplastic meningitis associated with B-cell malignancies, is particularly important if cytology, immunocytochemistry, flow cytometry and automated gene scanning of CSF samples are unable to detect malignant monoclonal proliferation.

B-Lymphocytes↗
PubMed2003

Thymic export function and T cell homeostasis in patients with relapsing remitting multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory and possibly autoimmune mediated demyelinating disease of the CNS. Autoimmunity within the CNS may be triggered by dysfunction of peripheral immune tolerance mechanisms via changes in the homeostatic composition of peripheral T cells. We have assessed the release of naive T lymphocytes from the thymus in patients with relapsing remitting MS (RRMS) to identify alterations in the equilibrium of the peripheral T cell compartment. Thymic T cell production was estimated by measuring TCR excision circles (TRECs) as a traceable molecular marker in recent thymic emigrants. A total of 46 treatment-naive patients with active RRMS and 49 gender- and age-matched healthy persons were included in the study. The levels of TREC-expressing CD4(+) and CD8(+) T lymphocytes were significantly decreased in MS patients, and TREC quantities overall matched those of 30 years older healthy individuals. The average concentrations of TRECs/10(6) CD4(+) and CD8(+) T lymphocytes derived from MS patients and healthy donors were 26 x 10(3)/10(6) and 28 x 10(3)/10(6) vs 217 x 10(3)/10(6) and 169 x 10(3)/10(6), respectively. To account for any influence of T cell proliferation on TREC levels, we assayed T lymphocytes from additional patients with MS and normal individuals for telomere length (n = 20) and telomerase activity (8 MS patients, 16 controls), respectively. There were no significant differences between CD4(+) and CD8(+) T cells from MS patients and controls. Altogether, our findings suggest that an impaired thymic export function and, as a consequence, altered ability to maintain T cell homeostasis and immune tolerance may play an important pathogenic role in RRMS.

Acute Disease↗
PubMed2002

Inducible nitric oxide synthase and argininosuccinate synthetase: co-induction in brain tissue of patients with Alzheimer's dementia and following stimulation with beta-amyloid 1-42 in vitro.

In Alzheimer's disease (AD), amyloid plaques within the brain are surrounded by activated glial cells (microglia and astrocytes). The mechanisms of glial activation and its effect on disease progression are not fully understood. Growing evidence suggests that beta-amyloid (Abeta) peptide, a major constituent of the amyloid plaque, is critically involved in the induction of an inflammatory response. The goal of this study was to examine the role of Abeta in the pathogenesis of local inflammation and neuronal cell death. We found increased mRNA levels of inducible nitric oxide synthase (iNOS) and the arginine regenerating enzyme argininosuccinate synthetase (ASS) within cortices of AD patients suggesting high output NO production. In vitro, synthetic Abeta1-42 and to a lesser extent Abeta1-40 induced iNOS and ASS transcription with consecutive NO overproduction in mixed rat neuronal-glial cultures. Furthermore, Abeta-stimulation lead to an increased release of inflammatory cytokines interleukin (IL)-1beta, IL-6 and tumor necrosis factor-alpha. Again, Abeta1-42 had a much more pronounced effect as compared to Abeta1-40. Our data suggest that Abeta1-42 is a key mediator of glial activation and via the induction of inflammatory mediators may be a critical component of the neurodegenerative process in AD.

Aged↗
PubMed2002

Experimental herpes simplex virus encephalitis: inhibition of the expression of inducible nitric oxide synthase in mouse brain tissue.

In the brain tissue of 36 mice infected with herpes simplex virus type 1, strain F, we determined the expression of inducible nitric oxide synthase (iNOS) with semiquantitative reverse transcription polymerase chain reaction. The viral burden was quantitated by polymerase chain reaction. Nitric oxide, induced by iNOS, may contribute to neuronal cell damage following virus infection. As the experimental therapeutic strategy in herpes simplex virus encephalitis (HSVE), we used: N-nitro-L-arginin (L-NA), a selective inhibitor of iNOS; and combination therapies of either methylprednisolone/acyclovir or L-NA/acyclovir. The viral burden peaked in acute disease, and then returned to a low baseline value, except in untreated controls. The expression of iNOS mRNA was suppressed by L-NA and by acyclovir/corticosteroids. INOS inhibition may provide an additional therapeutic strategy targeted specifically to suppress iNOS expression as a potential secondary mechanism of tissue damage in acute and chronic HSVE.

Acyclovir↗