Activated suppressor cell function in multiple sclerosis--clinical correlations.

Activated suppressor cell function mediated by either freshly isolated peripheral blood mononuclear cells (MNCs), freshly isolated CD8+ lymphocytes or by CD8+ cell lines, has previously been found to be reduced compared to controls in multiple sclerosis (MS) patients with progressive disease (MS-P). In this study, we found that suppressor activity mediated by CD8+ cell lines, derived from MS patients with stable disease (MS-S) patients and maintained in culture for 14 days, was significantly greater (45 +/- 6%) compared to that mediated by MS-P patients' CD8+ cells (11 +/- 4%, P less than 0.005).

HLA antigens in narcolepsy.

Eighteen black patients with narcolepsy underwent human leukocyte antigen (HLA) typing. Eleven of the 18 had cataplexy. Twelve patients (66.

Rejection of fetal neocortical neural transplants by H-2 incompatible mice.

In order to examine questions concerning immunologic privilege of the central nervous system, we placed neocortical transplants into cerebral ventricles of mice. We compared the fates of transplants between fully H-2 compatible (isografts) and H-2 incompatible (allografts) animals. Histologic evaluation comparing animals from iso- and allograft groups revealed significant differences in the number of inflammatory cells and in the degree of necrosis within the grafts.

Late denervation in patients with antecedent paralytic poliomyelitis.

The development of new weakness, fatigue, and pain decades after acute paralytic poliomyelitis is a recognized syndrome. We conducted a controlled study of this syndrome by analyzing clinical, electromyographic, and muscle-biopsy features in 18 patients with a history of poliomyelitis--13 reporting 1 to 20 years of new weakness and 5 without new symptoms. The patients with new weakness also reported new muscle atrophy (9 of 13) and fatigue (10 of 13), symptoms not reported by the controls.

Susceptibility of astrocytes to class I MHC antigen-specific cytotoxicity.

Cell-mediated immune mechanisms contribute to tissue injury within the central nervous system (CNS) in a number of experimental diseases, including experimental allergic encephalomyelitis and some viral infections, and may mediate lesion formation in multiple sclerosis. We investigated the conditions under which murine astrocytes can become susceptible targets of cytotoxic T cells. We demonstrate that mouse astrocytes in vitro can be susceptible targets of class I major histocompatibility complex (MHC)-specific cytotoxicity mediated by L3 cytotoxic T lymphocytes (CTL).

Dexamethasone suppression test abnormalities in multiple sclerosis: relation to ACTH therapy.

We studied the 1-mg overnight dexamethasone suppression test (DST) in patients with MS. In about 50% of patients, serum cortisol did not fall below 5.0 micrograms/dl.

Molecular analysis of the CD8 gene in multiple sclerosis.

Analysis of DNA fragments of the CD8 gene following digestion with three restriction enzymes showed no differences between patients with chronic progressive multiple sclerosis (MS), familial MS and controls. These abnormalities suggest that any abnormalities in the expression of CD8 protein in MS are not likely to be due to a gross deletion or rearrangement of the CD8 gene.

An in vivo and in vitro analysis of systemic immune function in mice with histologic evidence of neural transplant rejection.

Histologic and immunocytochemical analyses of fetal neocortical tissue transplanted to the lateral ventricle of inbred adult mice indicate that this tissue survives transplantation well if the donor and host are isogeneic. The major histocompatibility complex (MHC) of the mouse is known as the H-2 locus. H-2-incompatible neural transplants (allografts), unlike their H-2-identical counterpart (isografts), are characterized by the presence of T cells comprising both major T-cell subsets and macrophages, and by a marked increase in the expression of both class I and class II (Ia) MHC antigens.

Defective suppressor cell function mediated by T8+ cell lines from patients with progressive multiple sclerosis.

Activated suppressor cell function, induced with either concanavalin A or OKT3 and mediated by either unfractionated mononuclear cells or "panning" enriched T8+ cells, freshly isolated from peripheral blood, is reduced in patients with progressive multiple sclerosis (MS) as compared with control donors. In this study, we generated T8+ cell lines from the peripheral blood of these same patients and controls. Suppressor activity, mediated by T8+ cells exposed to OKT3 on days 1, 7, and 14 of culture and then treated with mitomycin C on day 16, was significantly reduced in the MS group (mean percent suppression 13% +/- 5) as compared with the control group (68% +/- 6, n = 8, p less than 0.

Neuroleukin: a lymphokine product of lectin-stimulated T cells.

Neuroleukin is a lymphokine product of lectin-stimulated T cells that induces immunoglobulin secretion by cultured human peripheral blood mononuclear cells. Neuroleukin acts early in the in vitro response that leads to formation of antibody-secreting cells, but continued production of immunoglobulin by differentiated antibody-secreting cells is neuroleukin-independent. Although the factor is not directly mitogenic, cellular proliferation is a late component of the response to neuroleukin.

Comparison of T8+ cell-mediated suppressor and cytotoxic functions in multiple sclerosis.

Patients with progressive multiple sclerosis (MS) and controls were compared with regard to: (a) in vitro pokeweed mitogen (pwm)-induced IgG secretion, as an indirect measure of T8+ cell-mediated suppressor function; (b) alloantigen-directed cytotoxic activity, a predominantly T8+ cell-mediated function. The MS group had increased IgG secretion (4790 +/- 372 ng/ml vs. 1866 +/- 233 ng/ml, P less than 0.

Suppressor and cytolytic cell function in multiple sclerosis. Effects of cyclosporine A and interleukin 2.

Patients with progressive multiple sclerosis (MS) demonstrated persistent reductions in levels of concanavalin A (Con A)-induced suppressor activity and heightened levels of in vitro pokeweed mitogen (PWM)-induced IgG secretion. The reduced Con A suppressor activity could not be reversed by addition of interleukin 2 (IL-2). Cyclosporine A (CsA) treatment did not alter the defect in Con A-induced suppressor activity, but did markedly inhibit T8+ cell-mediated alloantigen directed cytolytic activity; this latter defect was reversible by in vitro addition of IL-2.

Activated suppressor cell dysfunction in progressive multiple sclerosis.

Concanavalin A (Con A)-induced suppressor activity has previously been shown to be reduced in multiple sclerosis (MS) patients with active clinical disease. In this study, we demonstrate that OKT3, as well as Con A induced suppressor activity mediated by unfractionated peripheral blood mononuclear cells is reduced in patients with the progressive form of MS. By performing reconstitution experiments involving E+, T4+, or T8+ cells derived from either MS patients or controls, and normal allogeneic macrophages or E- cells, we sought to define the cellular basis for this suppressor defect.

An epitope shared by central nervous system myelin and peripheral blood macrophages.

Lewis rats were immunized with a homogenate of human spinal cord. Splenocytes from the immunized rats were fused with cells from the SP2/0-Ag14 cell line to form hybrids that were subsequently screened immunohistochemically for secretion of antibodies against myelin. Thirty hybrids secreting anti-myelin antibodies were cloned.

Dissociation of T8+ cell-mediated cytolytic and suppressor functions in young adults.

In the normal young adult population, in vitro levels of polyclonally-induced IgG secretion by mononuclear cells (MNCs) vary widely amongst individuals. Levels of IgG secretion correlate with functional suppressor activity of T8+ cells but not with their proportion within the MNCs either prior to culture, or as found in this study, at the end of the culture period. The current study also demonstrates a lack of correlation between T8+ cell-mediated suppressor (Ts) function and a second predominantly T8+ cell-mediated function, alloantigen-directed cytolytic (Tc) activity.

N-acetyl-beta-hexosaminidase beta locus defect and juvenile motor neuron disease: a case study.

A patient with partial deficiency of N-acetyl-beta-hexosaminidase (Hex) developed a progressive motor neuron syndrome beginning at age 7, characterized by dysarthria, muscle wasting, fasciculations, and pyramidal tract dysfunction. Minor clinical features have included tremor and late distal sensory abnormalities. Rectal biopsy at age 24 demonstrated membranous cytoplasmic bodies in submucosal ganglion cells.

Glucocorticoid receptors in depression: relationship to the dexamethasone suppression test.

Cytoplasmic glucocorticoid receptor content wa quantitated in lymphocytes from unmedicated depressed patients and control subjects before and after a standardized dexamethasone suppression test. Depressed patients (N = 11) had significantly lower (32%) basal cytoplasmic glucocorticoid receptor content than the control group (N = 14). Suppression of serum cortisol (5.

Senile dementia of Alzheimer's type (SDAT): reduced T8+-cell-mediated suppressor activity.

We compared patients with senile dementia of the Alzheimer's type (SDAT) and age-matched controls with respect to T8+-cell-mediated suppressor function using a pokeweed mitogen (pwm)-induced IgG secretion assay. The responding B cells were allogeneic to the T-regulator cells. T8+-cell-mediated suppression was lower in SDAT patients than the controls when we used either 2 X 10(4) or 5 X 10(4) T8+ cells.

Generation of monoclonal antibodies recognizing neuronal elements in formalin-fixed paraffin-embedded human tissue.

We used formalin-fixed human spinal cord and dorsal root ganglia as immunogens to generate monoclonal antibodies (mAb) which immunohistochemically react with neurons in formalin-fixed human tissue sections. Three of the mAb recognized all neuronal populations studied, including those in spinal cord, dorsal root ganglia, cerebellum, and cerebrum. A fourth mAb recognized neurons within spinal cord, dorsal root ganglia and dentate nucleus of cerebellum but not those in cerebrum or cerebellar hemispheres.

N-acetyl-beta-hexosaminidase B deficiency in cultured fibroblasts from a patient with progressive motor neuron disease.

A patient with a 20-year history of progressive motor neuron disease was previously found to have profoundly low levels of N-acetyl-beta-hexosaminidase (Hex) in serum and leukocytes; Hex activity in cultured skin fibroblasts was in the low normal range. By thermal inactivation and cellulose acetate electrophoresis, the residual activity appeared to be Hex A. In the present study, the residual activity in cultured skin fibroblasts was further characterized as Hex A by thermal inactivation at reduced temperatures and ion exchange chromatography; no evidence was obtained for a diffusible inhibitor of Hex activity.