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We have studied immune regulation in MS using monoclonal antibodies against T cell subsets.We could confirm a decrease in the number of T suppressor cells in peripheral blood of 16 active MS patients (16.7%±1.7) when compared to 16 healthy controls (26.2±2.2 p

Background: Subclinical multiple sclerosis (MS) has been identified incidentally at autopsy; apparently unaffected individuals with an affected twin have demonstrated magnetic resonance imaging (MRI) changes consistent with MS, and ‘MRI relapses’ are several times more common than clinical relapses. Case description: A 39-year-o ld, right-handed man underwent MRI and PET scanning in 1986 as a ‘normal’ control in a Parkinson’s disease study, where his father was the proband. MRI indicated multiple areas of abnormal signal intensity in a periventricular and grey -white matter junction distribution. Repeated clinical evaluations over the next 10 years were unchanged until 1996, when he complained of progressive weakness of the right foot and clumsiness in the right hand. MRI now indicated a further area of high signal intensity in the right posterior cord at the level of C 5/C 6. There was mild pyramidal distribution weakness in the right leg with an extensor plantar response on the same side. O ver the next five years there has been mild progression in weakness and fatigue and intermittent Lhermitte’s phenomenon. A t no stage has there been a history of relapse, cerebrospinal fluid examination was normal and evoked responses (visual and somatosensory) are normal. Conclusion: This case demonstrates the pheno menon of subclinical MS, unusually supported by prolonged clinical and MRI follow-up. The patient eventually became symptomatic nine years after MRI diagnosis and is following a primary progressive course. A lthough MRI is known to be sensitive in identifying subclinical ‘attacks’, the pattern illustrated here may actually be quite typical of primary progressive MS and is compatible with the later onset seen in this subgroup of patients.

Baló's concentric sclerosis is a demyelinating disorder in which bands of demyelination alternate with concentric bands of myelin preservation. The pathogenesis of the lesion is unknown. Previous reports using modern histopathologic techniques have shown the bands of myelin preservation to be comprised of remyelinated or partially demyelinated myelin. Here we report a case of Baló's concentric sclerosis in a 24-year-old East Indian patient with a previous history of relapsing-remitting multiple sclerosis (MS). Pathologically, the bands of myelin preservation showed myelin sheaths of normal thickness, with focal areas of demyelination. The findings, taken together with those of previously reported cases, suggest that Baló's concentric sclerosis is a variant of MS, and the concentric lesion may be an intermediary form in evolution of a chronic active MS plaque. The pathogenesis of this concentric lesion may be explained by periodic suppression of demyelination in the rapidly expanding border, allowing remyelination or only transient incomplete demyelination to occur.

Background: Human T-cell lymphotropic virus 1 (HTLV-1) infection can lead to myelopathy/tropical spastic paresis and adult T-cell leukemia/lymphoma (ATLL). Infection with HTLV-1 has also been associated with clinically significant immunosuppression. Crusted scabies, also known as Norwegian scabies, is an uncommon presentation of scabies that may occur in conjunction with immunosuppression. Although crusted scabies has been reported in association with HTLV-1 infection, to our knowledge it has never been described in association with HTLV-1 associated myelopathy. Objective: The aim is to describe a case of HTLV-1 associated myelopathy and concomitant crusted scabies. Methods: This article includes a case report and a literature review. Conclusions: Crusted scabies is reported in association with HTLV-1 infection with or without concomitant ATLL. Crusted scabies should be considered in the differential diagnosis of a generalized cutaneous eruption in an HTLV-1 positive patient. Patients with crusted scabies from an HTLV-1 endemic population should be tested for a possible HTLV-1 infection. These patients may be at increased risk of progressing to ATLL.

To correlate computed tomographic (CT) appearance of the thymus with results from histologic examination of thymic tissue and clinical outcome in patients with generalized myasthenia gravis who underwent thymectomy.Forty-five patients with myasthenia gravis underwent CT of the thorax and thymectomy. Findings at clinical follow-up were available in all patients.Twenty-six patients had normal CT findings, seven had a diffusely enlarged thymus, and 12 had a focal mass. The results of histologic examination showed that 16 of 26 patients with normal CT findings had normal thymic tissue and 10 had lymphoid follicular hyperplasia; all seven patients with an enlarged thymus had lymphoid hyperplasia. Five of 12 patients with a focal mass at CT had lymphoid hyperplasia, and seven had thymoma. Clinical improvement following thymectomy was observed in 27 (93%) of 29 patients with lymphoid hyperplasia or thymoma and 11 (69%) of 16 patients with normal histologic examination (P.03, chi(2) test).The presence of an enlarged thymus or a focal mass in patients with myasthenia gravis indicates lymphoid hyperplasia or thymoma. However, CT is of limited value in distinguishing lymphoid follicular hyperplasia from a normal thymus or thymoma and in predicting clinical outcome.

We describe eight patients with associated multiple sclerosis (MS) and myasthenia gravis (MG). Patients were less than 50 years old at the time of onset, and seven were female. The clinical course of both MS and MG was mild in most patients. To our knowledge, this represents the largest reported series. We provide further evidence for a nonrandom association of these two diseases and discuss common mechanisms of patho genesis.

Age-related changes in the processes involved in T cell dependent polyclonal B cell activation in man were studied by comparing immunoglobulin (Ig) produced in autologous T:B (E + :E − ) cell cultures of young and old donor pairs with Ig produced in crossover cultures. Each young and old donor was classified as a responder or a non-responder based on Ig levels in autologous pokeweed mitogen-activated T:B cultures. The data indicate that: (1) T suppressor influences are a major determinant of non-response in the young; (2) T cells of nonresponder old donors can support high levels of Ig secretion by young donors' B cells; (3) low response to pokeweed mitogen stimulation in the elderly may reflect either direct refractoriness of B cells to T cell dependent stimulation, heightened B cell sensitivity to suppressor signals, or a combination of the two.

Neutralizing (Nt) antibodies to poliovirus types 1, 2 and 3, and to mumps virus, were measured in sera from 27 patients with amyotrophic lateral sclerosis, and from 28 age- and sex-matched controls. No significant differences were observed in distribution or in geometric mean titers of antibodies, when the two groups were compared.

Bacteriophage immunoassays, radioimmunoassays, and biological assays have been used to measure levels of NGF in media conditioned by rat C-6 glioma cells in culture. By all three criteria, these cells secrete a macromolecule which is indistinguishable from mouse submandibular gland NGF.

Evidence points to the conclusion that abnormal regulation of the immune response in MS contributes to ongoing immune activity.

261 multiple sclerosis (MS) patients were HLA-A and -B typed and 94 were HLA-D typed. The results were compared to those of controls typed for HLA-A; HLA-B (356) and HLA-D (113). We confirm and extend earlier findings (Oger et al. 1980b) that some phenotypes could modulate the expression of the MS susceptibility gene linked to B7-DR2: DR3 was found together with DR2 in 12/94 MS and only 3/113 controls and could be marker for an "augmentor" gene. In contrast, B35 and DR1 as well as B12 and DR7 could be markers of protector genes. We compared typing results of patients subgrouped on clinical features. 61 patients with progressive evolution showed increased A1, A1-B8, B8-DR3 and A1-B8-DR3 when compared to 200 patients with remitting evolution. When compared to controls both groups showed increased B7 but only the remitting group showed increased DR2. 71 patients with "benign MS" showed increased B7-DR2 and A3-B7-DR2. 54 patients with "severe disease" showed increased DR3 and A1-B8-DR3 when compared to controls. Both groups showed increased B7 (49.2% and 44.4% versus 25.5% for controls). 120 patients treated greater than 5 years with azathioprine were divided into "no progression" and "progression" while treated. Both groups showed increased B7 when compared to controls. DR2 was increased only in the "no progression" group. B8-DR3 and A1-B8-DR3 were found increased in the "progression" group only. We conclude that two forms of MS exist with different HLA profiles.

In vitro modulation of human T lymphocyte surface differentiation antigens T3, T8, and T4, by their respective monoclonal antibodies, was studied as a function of donor age. Kinetic studies performed on lymphocytes from young adults indicated that modulation is dependent on concentration of antibody used and duration of culture. OKT3 modulates T3 rapidly (maximum at less than 24 hr) and relatively completely (79% at the highest concentration of antibody used). By 48 hr, regeneration of the T3 antigen is apparent. T8 modulation by OKT8 is slower (continued modulation at 48 hr) and less complete than is T3 modulation by OKT3. OKT4 does not modulate the T4 antigen. In elderly individuals modulation of T3 by OKT3 is preserved whereas modulation of T8 by OKT8 is significantly reduced (24 ± 8% at 48 hr vs 53 ± 4% for young controls). These observations document further age-related changes in properties of human T suppressor cells.

The role of cell-mediated immunity (CMI) in the pathogenesis of idiopathic polyneuritis (IP) is discussed. Of significance has been the finding of a decreased suppressor T cell response in IP. This may provide an important common denominator linking the numerous antecedent events which trigger IP to the disease. The role of humoral immunity in IP and chronic relapsing inflammatory polyneuritis (CRIP) remains controversial, but has awakened renewed interest in view of recent reports of favorable response to plasmapheresis in IP and CRIP patients. P2 protein is an important neuritogenic factor in experimental allergic neuritis (EAN), but we failed to find antibody directed against P2 in either IP or CRIP even though anti-P2 antibody was regularly detected in EAN. Whether CMI response to P2 occurs in IP or CRIP remains controversial. We did not detect CMI response to P2 in IP or CRIP. It may be that the neuritogenic factor (or factors) in IP and CRIP remains to be found.

In vitro Ig secretion by peripheral blood mononuclear cells (MNCs) from old and young donors, in response to T-dependent (TD) [pokeweed mitogen (PWM)] and T-independent (TI) [ Salmonella paratyphii B (SPB)] activation were compared. In older donors, the IgG and IgA responses to PWM were comparable to those of young donors; the IgM response was reduced in the elderly. With SPB activation, IgA response was again preserved, whereas IgG response was reduced and IgM secretion was markedly decreased. These data indicate class-specific changes in Ig responsiveness to both TD and TI cell activators with age. The reduction in TI-induced IgG and IgM responses in the elderly suggest that changes in B cells themselves have occurred. The preservation of the TD IgG response in concert with reduced TI response indicates that a decline in T-suppressor influences over B cells in the elderly coupled with reduced B-cell synthesizing capacity can result in apparent “preservation” of the final Ig response. In keeping with the above postulate, analysis of individual elderly donors' responses indicated that some of the old donors responded to PWM, but not SPB; none of the old donors responded to SPB and not PWM. In contrast, some young donors did respond to SPB, but not PWM. These results also suggest that nonresponse to PWM in young donors relates to an override of functionally intact B cells by T-regulator influences.

The selective reduction of PAM cell yield reported by Carp and associates in the presence of tissue from patients with multiple sclerosis (MS) has been attributed to replication in culture of a viral agent associated with MS (MSAA). We investigated the diagnostic potential of the PAM cell effect in MS and in optic neuritis (ON). Six serum and 7 CSF samples from 7 patients with MS, 3 serum and 3 CSF samples from 4 patients with idiopathic ON, and 4 sera from 4 patients with ON induced by ethambutal toxicity were tested. Blind counting showed no reduction in PAM cell yield in the MS group nor any significant difference between the two ON groups. Disturbing inconsistencies in PAM cell growth rates over time and between control flasks were demonstrated.

The mechanisms underlying reduced T-cell mitogenic reactivity which accompany human aging were explored in vitro using concanavalin A (Con A) to induce cell proliferation. Peak mitogenic reactivity of both unfractionated mononuclear cells (MNCs) and purified E + cells from elderly donors was reduced compared to the corresponding cell populations from young individuals. Flow cytometric studies demonstrated that the number of cells entered into the cell cycle at the time of maximum mitogenic stimulation was reduced in the elderly. Peak response to Con A of E + cells from young donors cocultured with monocytes from old individuals matched that obtained when these cells were cocultured with monocytes from young donors. The response to Con A of cocultures of monocytes from young donors and E + cells of old donors merely matched the reactivity of old donors' MNCs. These data indicate that changes in intrinsic T-cell properties alone account for the reduced proliferative capacity in the elderly.

Selected properties of peripheral blood lymphocytes (PBLs) from five ambulatory affected individuals of a kindred with autosomal dominant cerebrovascular amyloidosis were studied. The percentage of PBLs bearing surface membrane immunoglobulin (SmIg+ cells) was increased in the patient group (30 +/- 3% versus 20 +/- 2%; p less than 0.05). The percentage of PBLs forming early and total E-rosettes was comparable in patient and control groups. Mitogenic response to concanavalin A (Con A) was suggestively reduced in the patient group, measured both by total 3H-thymidine incorporation and by comparison of stimulation indices. Mitogenic response to phytohemagglutinin and pokeweed was comparable in the two groups. Capping of Con A by PBLs was significantly reduced in the patient group compared with the controls (13 +/- 1% versus 26 +/- 2%; p less than 0.01). The findings of reduced Con A response and increased SmIg+ cells support the hypothesis that immune dysfunction contributes to the development of amyloidosis. The reduced capping suggests altered membrane properties in this autosomal dominant disorder.

The proportion of MS patients whose pokeweed mitogen-stimulated mononuclear cells (MNCs) secreted greater than 1,000 ng/ml IgG per 10(6) cells (ie, "high responders") was increased compared with controls. The suppressor effect mediated by a constant number of T8+ cells from high responders, both MS and control, on IgG secretion by standard T helper (T4+) plus B-cell cultures was significantly lower than that for the same number of T8+ cells from "low responders." The proportion of T8+ cells within MNCs from MS patients did not correlate with levels of IgG secretion. Our results indicate that high levels of IgG secretion by MNCs, an occurrence overrepresented in the MS population, is significantly influenced by functional properties of T suppressor cells.

The increase in frequency of tissue types A3 and B7, accompanied by a decreased frequency of B12 in persons afflicted with MS and of North European Caucasian extraction appears established [2, 5, 17, 22]. The augmentation found is modest, however, (relative risk 1.2 to 1.7) and the considerable variation between the results of individual studies should be noted. These discrepancies between laboratories may be partly explainable based on differing specificities of antisera used to detect HLA types and the difficulties inherent in obtaining consistent diagnostic criteria, particularly in the case of large series involving cooperation among several centers. The linkage disequilibrium between A3 and B7 which is characteristic of the North European Caucasian population as a whole has been found to be exaggerated in MS victims [6, 17]. This may suggest that a gene in linkage disequilibrium with A3-B7 on chromosome 6 may have a major role in the development of the disease.

The cardinal pathological feature of multiple sclerosis (MS) is the presence within brain and spinal cord of regions called plaques, from which myelin has been lost1. It has been proposed that autoimmunity may be involved in MS and that oligodendrocytes, the cells responsible for the formation and maintenance of central nervous system myelin, may provide a target for immune attack in this disease. The fact that oligodendrocytes are reduced in number in MS plaques2 is consistent with this hypothesis. MS is characterized by attacks and remissions. During attacks, a subset of T lymphocytes, known as T suppressor cells, is depleted from the circulation3–5. The reason for this depletion is unknown, but the suppressor cells could be destroyed, sequestered, for example in brain, or modulated so that they are no longer detectable by the assays which enumerate them or which measure their functional capacities. Were suppressor cells and oligodendrocytes to share a determinant relevant to MS, both cell types could be targets for immune-mediated killing by the same autoimmune response. Recently, monoclonal antibodies which recognize human monocytes, T lymphocytes and T-cell subsets have become available. We have tested cultured ovine oligodendrocytes with a battery of monoclonal antibodies directed against human lymphocyte and monocyte antigens, seeking evidence for shared determinants, and present here data suggesting that shared determinants exist.

Normal primary chick embryo fibroblast cultures product a nerve growth-promoting factor which cross-reacts with monospecfic antibody to pure male mouse submaxillary gland nerve growth factor (NGF). When taken together with the earlier demonstration that mouse L2 CELLS AND 3T3 cells also produce an NGF-like protein, these findings suggest that secretion of this factor may be a general property of fibroblast.