Antigen presentation by autoreactive proteolipid protein peptide-specific T cell clones from chronic progressive multiple sclerosis patients: roles of co-stimulatory B7 molecules and IL-12.

To assess the role of T cell antigen (Ag) presentation in multiple sclerosis (MS), proteolipid protein (PLP) peptide reactive CD4+ T cell clones (TCCs) from MS patients and normal subjects were studied. TCCs derived from chronic progressive (CP) MS patients were able to proliferate and secret cytokines in response to PLP peptide stimulation in the absence of professional antigen presenting cells (APCs), suggesting that these T cells can simultaneously present and respond to Ags. However, they did not respond to total PLP protein, suggesting that PLP-peptide TCCs were unable to process and present the whole PLP molecule.

Effect of estradiol on cytokine secretion by proteolipid protein-specific T cell clones isolated from multiple sclerosis patients and normal control subjects.

The ability of estradiol (E2) to modulate the secretion of cytokines by CD4+ T cells was investigated using neuroantigen-specific T cell clones isolated from normal control subjects and patients with the demyelinating disease, multiple sclerosis. In the presence of E2, the majority of the tested clones showed a dose-dependent enhancement of Ag-stimulated IL-10 secretion. The secretion of IFN-gamma was also enhanced, although the peak enhancement occurred at lower E2 concentrations and at lower magnitude than observed for IL-10.

Defective post-thymic tolerance mechanisms during the chronic progressive stage of multiple sclerosis.

We have recently isolated a panel of T-cell clones from chronic progressive multiple sclerosis (MS) patients that are capable of functioning as antigen-presenting cells and of expressing the costimulatory molecules B7-1 and B7-2. In this report we show that these T-cell clones are resistant to inhibitory regulation, including the induction of anergy and sensitivity to tumor growth factor-beta (TGF-beta)-induced growth inhibition. The resistance to anergy induction was associated with expression of B7 costimulatory molecules.

Insulin and angiotensin II are additive in stimulating TGF-beta 1 and matrix mRNAs in mesangial cells.

Angiotensin II (Ang II) and insulin are implicated in the mesangial cell hypertrophy and excessive accumulation of mesangial matrix seen in glomerulosclerosis. Therefore, the effects of Ang II with and without insulin on mRNA levels of several important extracellular matrix genes and transforming growth factor beta-1 (TGF-beta 1) were examined. Ang II alone (1 microM) added to quiescent, murine mesangial cells in serum-free, insulin-free media slightly but not significantly increased TGF-beta 1, fibronectin, collagen I, collagen IV and laminin message levels.

Neuron-specific enolase, a marker of acute neuronal injury, is increased in complex partial status epilepticus.

Purpose: To determine whether complex partial status epilepticus (CPSE) causes brain injury in humans. Serum neuron-specific enolase (s-NSE) is an accepted marker of acute brain injury, and increases in s-NSE have been correlated with the duration and outcome of generalized convulsive status epilepticus. s-NSE levels in CPSE are unknown.

Neuron-specific enolase is increased after single seizures during inpatient video/EEG monitoring.

Neuron-specific enolase (NSE) is a marker of brain injury after acute neurologic insults. We report changes in serum NSE (s-NSE) in 25 patients (15 with epilepsy and 10 patients with nonepileptic events) during continuous inpatient video/EEG monitoring. s-NSE was significantly increased as compared with baseline and normal controls after the first ictal event in the epileptic group, especially in patients with secondarily generalized tonic-clonic seizures (p = 0.

Isolation and characterization of autoreactive proteolipid protein-peptide specific T-cell clones from multiple sclerosis patients.

During the course of multiple sclerosis (MS), myelin proteins are likely antigenic targets for autoreactive T cells. Although most studies have implicated myelin basic protein as a potent encephalitogenic myelin component, proteolipid protein (PLP) appears also to be a possible target antigen in the autoimmune response in MS. In this report, we investigated the human T-cell responses to PLP by using PLP104-117 and PLP142-153 synthetic peptides as target antigens in limiting dilution.

Serum neuron-specific enolase in human status epilepticus.

Neuron-specific enolase (NSE) is a sensitive marker of brain injury after stroke, global ischemia, and coma. We report changes in serum NSE (s-NSE) in 19 patients who sustained status epilepticus. s-NSE peaked within 24 to 48 hours after status epilepticus.

Neuron-specific enolase is increased after nonconvulsive status epilepticus.

Serum neuron-specific enolase (s-NSE), a marker of brain injury and acute seizures, was increased in 2 patients with nonconvulsive SE. Neither patient had an acute neurologic insult other than nonconvulsive SE (NCSE) accounting for s-NSE changes. Increase in s-NSE provides further in vivo evidence of transient brain injury after NCSE.

Patterns of cytokine secretion by autoreactive proteolipid protein-specific T cell clones during the course of multiple sclerosis.

To determine whether cytokine secretion patterns change with disease status in patients with multiple sclerosis (MS), we measured IFN-gamma, TNF-alpha beta, IL-4, IL-6, IL-10 and TGF-beta secretion in a panel of T cell clones (TCCs) specific for proteolipid protein (PLP) after stimulation with PLP peptides or polyclonal activators. During acute attack, the predominant pattern of cytokine secretion resembled that of murine Th1 cells; i.e, IFN-gamma and TNF-alpha beta, and appeared to be restricted to PLP-reactive TCCs.

Effect of persistent mouse hepatitis virus infection on MHC class I expression in murine astrocytes.

Neurotropic strains of mouse hepatitis virus (MHV) have been used extensively for the study of viral pathogenesis in the central nervous system (CNS), serving as models for human neurological diseases such as multiple sclerosis (MS). MHV strains A59 and JHMV both cause acute and chronic encephalomyelitis and demyelination in susceptible strains of mice and rats. In acute disease, CNS damage is most likely the result of lytic infection in neurons and oligodendrocytes, and death can be prevented by the adoptive transfer of Class I-restricted CD8+ T cells.

Coronavirus induction of class I major histocompatibility complex expression in murine astrocytes is virus strain specific.

Neurotropic strains of mouse hepatitis viruses (MHV) such as MHV-A59 (A59) and MHV-4 (JHMV) cause acute and chronic encephalomyelitis and demyelination in susceptible strains of mice and rats. They are widely used as models of human demyelinating diseases such as multiple sclerosis (MS), in which immune mechanisms are thought to participate in the development of lesions in the central nervous system (CNS). The effects of MHV infection on target cell functions in the CNS are not well understood, but A59 has been shown to induce the expression of MHC class I molecules in glial cells after in vivo and in vitro infection.

CSF neuron-specific enolase after methohexital activation during electrocorticography.

We report changes in CSF and serum neuron-specific enolase (NSE) before and after methohexital infusion during electrocorticography in three patients undergoing epilepsy surgery. NSE is a critical enzyme for energy metabolism that accounts for 1.5% of all soluble brain protein and is an accepted marker of neuronal injury.

Increased systemic B- and T-lymphocyte responses in hereditary motor and sensory neuropathy (HMSN I).

Immune mechanisms of possible importance for the development and maintenance of peripheral nerve myelin breakdown in HMSN I were analysed by measuring B- and T-cell activation in blood, bone marrow and cerebrospinal fluid. Patients with polyneuropathies of other etiologies served as one control group and patients with tension headache as another. Flow cytometry of blood and bone marrow mononuclear cells revealed that an increased number of CD3+, CD4+ and CD4- CD8- T-cells expressed a late stage activation marker (Ta1).

Calcium antagonists suppress experimental allergic neuritis (EAN).

We examined the influence of Ca++ antagonist drugs on immune response and the clinical course of experimental allergic neuritis (EAN). The Ca++ antagonists verapamil and flunarizine suppressed actively induced EAN in Lewis rats in a dose-dependent fashion when given continuously by osmotic pumps from the day of immunization. If given from onset of clinical signs, day 10 after immunization, verapamil alone had therapeutic effects.

Effect of stilbene-type anion channel blockers on the immune response during experimental allergic neuritis (EAN).

We have studied the role of anion channel gating for the autoimmune response in experimental allergic neuritis (EAN) induced by bovine peripheral myelin (BPM). The influence of the stilbene-type anion channel blockers SITS and DIDS on T cell function was assessed by measurement of proliferation and by counting of interferon-gamma (IFN-gamma) secreting cells (IFN-gamma-sc) in response to BPM and phytohemagglutinin (PHA). SITS caused a dose-dependent increase of spontaneous proliferative activity as well as of proliferation in response to the antigenic stimulus BPM.

Sulfasalazine aggravates experimental autoimmune encephalomyelitis and causes an increase in the number of autoreactive T cells.

Sulfasalazine (SASP; 5-(p-(2-pyridylsulfamoyl)phenylazo)salicyclic acid) has beneficial effects on certain inflammatory diseases and has been proposed for clinical trials in multiple sclerosis (MS). We have explored the effects of SASP on actively induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats. SASP was given orally at three different doses from the day of immunization to day 40 post-immunization (p.

Cell cycle-dependent expression of CD4 antigen in a monocytoid cell line.

The CD4 molecule has several biological functions, physiologically as a receptor for major histocompatibility complex class II molecules on antigen-presenting cells, and pathologically as a receptor for human immunodeficiency virus (HIV) by its binding to the HIV envelope glycoprotein gp 120. The frequency of CD4+ cells has been shown to correlate positively with both susceptibility and cytopathogenic effect by HIV. To determine if CD4 expression varied during the cell cycle, a CD4-expressing monocytoid cell line, U 937 clone 16, was synchronized with regard to cell growth.

CD5+ B cells and CD4-8-T cells in neuroimmunological diseases.

Using 2- and 3-colour FACS analysis we found increased levels of fetal-type CD5+ B cells and CD4-8- T cells in cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and aseptic meningitis (AM) compared to control probands with muscular tension headache (TH). Similar differences were found for CD5+ B cells in peripheral blood, but at lower levels. CD4-8- T cells in blood exceeded those in CSF in all patient groups, with the exception of relapsing remitting MS, revealing the highest values in AM.

Peripheral nervous system and spinal cord involvement in lymphoma.

Nine-hundred-eighty-nine patients with diagnosis of lymphoma were studied. Forty-six cases (4.6%) had compressions of the spinal cord or roots.

Craniocerebral involvement in lymphoma.

Nine-hundred-eighty-nine patients with lymphoma were studied. Fifty-three cases (5.3%) had lymphomatous craniocerebral infiltration.

CD4+, CD8+, and CD4- CD8- T cells in CSF and blood of patients with multiple sclerosis and tension headache.

Two-colour flow cytometric analysis was performed on paired samples of peripheral blood (PB) and cerebrospinal fluid (CSF) of patients with untreated multiple sclerosis (MS) and, for reference, subjects with muscular tension headache (TH) using anti-CD3, anti-CD4, anti-CD8, and anti-HLA-DR monoclonal antibodies in different combinations. CD4+/CD8+ T-cell ratio was increased in CSF compared to PB in both MS patients and TH subjects to a similar extent. This was mainly due to higher CD4+ T-cell levels in the CSF compartment.

B cells expressing CD5 are increased in cerebrospinal fluid of patients with multiple sclerosis.

By two-colour flow cytometric analysis, we found increased numbers of B cells co-expressing the pan-T cell marker CD5 and the B cell marker CD19 in cerebrospinal fluid (CSF) of 21 patients with multiple sclerosis (MS), compared with 17 control subjects with muscular tension headache. Only one patient with MS, but nine controls lacked CD5+ B cells in CSF. This difference was not observed in peripheral blood.

Neuromuscular transmission studies in human chronic Chagas' disease.

An electrophysiological investigation of the state of the neuromuscular transmission (nmt) was carried out in 58 patients with the diagnosis of chronic Chagas' disease. On repetitive supramaximal nerve stimulation it was found that some patients did not show abnormalities, others had decremental muscle responses, others developed enhancement of the muscle evoked potential amplitudes, while some other patients combined both types of pathological responses. The findings suggest that some patients with chronic Chagas' disease develop impairment of nmt, though data obtained in this study do not give information about neither the type of impairment nor the localization (pre or postsynaptic, or both) of the damage.

Cerebral evoked potentials in human chronic Chagas' disease.

Seventy five patients with the diagnosis of chronic Chagas' disease were studied by employing EPs techniques. Two of them had delayed arrival of the signal to the Erb's point and one to the spinal cord when looking at SEPs. Two patients had increment of the time interval between waves Ist and IIIrd, when studying PEATs.