The B-cell response to myelin and myelin basic protein was studied in patients with multiple sclerosis and in patients with acute aseptic meningoencephalitis by using a nitrocellulose immunospot assay. This method allows detection of single cells producing antibodies. Twenty-seven (79%) of 34 patients with multiple sclerosis had cells producing IgG antibodies against myelin, and 11 (57%) of 19 had cells producing IgG antibodies against myelin basic protein in cerebrospinal fluid (CSF), with mean values of 30 and 14 per 10(4) mononuclear cells, respectively. Total numbers of IgG-producing cells occurred at a mean number of 75 per 10(4) CSF cells. Cells producing antimyelin or anti-myelin basic protein antibodies of IgA or IgM isotypes were rarely found in CSF. Patients with acute aseptic meningoencephalitis less frequently showed CSF cells producing IgG antibodies against myelin and myelin basic protein. No cells producing antibodies against myelin or myelin basic protein were detected in peripheral blood of patients with multiple sclerosis or meningoencephalitis. Thus, a majority of patients with multiple sclerosis had CSF cells that produced IgG antibodies against myelin and myelin basic protein. These cells comprised a large proportion of the total IgG-producing cells. A pronounced B-cell response against autoantigens produced at the target for immune attack might be important in the pathogenesis of multiple sclerosis.

Adult↗

PubMed1990

Detection of intracellular expression and secretion of interferon-gamma at the single-cell level after activation of human T cells with tetanus toxoid in vitro.

Activation of T cells results in intracellular expression and secretion of cytokines such as interferon (IFN)-gamma. Here we have used three different assays for determination of IFN-gamma in tetanus toxoid- or mitogen-activated human T cell cultures. Two of these assays [intracytoplasmic immunofluorescence and enzyme-linked immuno spot assay (ELISPOT)] determined the expression and secretion of IFN-gamma at the single-cell level while the third assay enzyme-linked immunosorbent assay (ELISA) measured IFN-gamma secreted into the culture supernatant. Comparison of all three tests revealed a good correlation between the ELISPOT assay and the ELISA, whereas expression of intracellular IFN-gamma showed a qualitative but not a quantitative correlation with the latter. Both the immunospot assay and the immunofluorescence may be used to detect approximate numbers of specific T cells even when present at low frequencies. With the use of the immunospot assay antigen-specific T cells could be detected even in the absence of detectable IFN-gamma in the culture supernatants. However, the ELISA assay should be more convenient for screening large clinical material.

Antigens↗

PubMed1990

Prognosis after stroke in diabetic patients. A controlled prospective study.

Cohorts of diabetic (n = 121) and non-diabetic (n = 584) patients were prospectively followed for up to ten years after having suffered from a stroke. All but six of the diabetic patients had Type 2 (non-insulin-dependent) diabetes mellitus. The diabetic patients had more risk factors associated with stroke: heart failure (p less than 0.001) and angina pectoris (p less than 0.001), than the non-diabetic patients. Neither body mass index nor blood pressure levels differed between the groups at admission. Haematocrit levels were higher in the diabetic group (p less than 0.01). The diabetic patients were more commonly afflicted by cerebral embolism and to a lesser extent by transient ischaemic attacks than the non-diabetic patients. When calculated by log-rank tests, the diabetic group had an increased risk of death (p less than 0.001), recurrent stroke (p = 0.001), and of myocardial infarction (p = 0.001) after the initial stroke. Autopsy-verified causes of death between the groups did not differ significantly, although half of all deaths during the period one to six months after stroke were caused by pulmonary embolism in the diabetic group. Thus, diabetes increases the risk of death after a stroke, and it also increases among stroke survivors the risk of recurrent stroke and myocardial infarction.

Cerebrovascular Disorders↗

PubMed1990

Persistent anti-myelin basic protein IgG antibody response in multiple sclerosis cerebrospinal fluid.

Antibodies to myelin components, such as myelin basic protein (MBP), may play a role in pathogenesis of multiple sclerosis (MS) but results from determinations of anti-MBP antibodies are inconsistent. Enumeration of cells secreting antibodies represents a new approach to evaluate a specific antibody response regarding extent and localization, and reduces effects of e.g. antibody binding to target. Anti-MBP IgG antibody secreting cells were present in MS patients' cerebrospinal fluid (CSF) at a mean value of 1 per 833 cells, and they amounted to a mean value of about 2454 in the whole CSF compartment. Similar numbers were encountered in patients with other inflammatory neurological diseases (OIND). During follow-up, anti-MBP IgG antibody secreting cells persisted regarding frequency and numbers in MS, but decreased in OIND. Such cells were rarely detected in patients with tension headache. No correlations to clinical exacerbation of MS, disability or duration were discernable. In blood from MS and OIND patients, anti-MBP IgG antibody secreting cells were detected infrequently and at low numbers. The anti-MBP antibody response is strongly restricted to the IgG isotype. The anti-MBP IgG antibody response which is persistent and compartmentalized to the diseased organ, may be important for the development of MS.

Adult↗

PubMed1990

Salivary cortisol during an overnight dexamethasone suppression test using a simple saliva collection device.

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Adult↗

PubMed1990

Depletion of CD8+ T cells suppresses growth of Trypanosoma brucei brucei and interferon-gamma) production in infected rats.

Sprague-Dawley rats infected with Trypanosoma brucei brucei showed a strong and rapid induction of splenocyte IFN-gamma (within 12 h post-infection) as measured by a single cell assay for IFN-gamma secretion. Depletion of CD8+ cells in infected rats abrogated the IFN-gamma production, suppressed parasite growth and increased survival of the animals. Induction of MHC class I antigens in the paraventricular and supra-optic hypothalamic nuclei caused by the trypanosome infection was also inhibited by the CD8+ cell depletion. It is suggested that the CD8+ cells are involved directly or indirectly in growth regulation of the parasite and that IFN-gamma induced by the parasite may be one of the factors that trigger MHC expression and immunosuppression.

Animals↗

PubMed1990

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. Numbers of CD5+19+ B cells were increased in CSF compared with blood in MS, but not in the controls. In both groups, CD5+19+ B cells were not restricted to small resting lymphocytes, but were also found among larger-sized lymphocytes. The relative density of CD5 molecules and of CD19 molecules was lower in CD5+19+ than in CD5-19+ B cells and CD5+19- T cells. CD5+ B cells are assumed to be responsible for autoantibody production, and our results suggest a pathogenetic role of such cells, predominantly within the central nervous system, in MS.

Adult↗

PubMed1990

Urinary free cortisol excretion shortly after ischaemic stroke.

The cortisol axis and catecholamine excretion were studied in 20 patients within the first week after acute ischaemic stroke. Urine free cortisol and plasma cortisol levels after dexamethasone were significantly higher in stroke patients than in 80-year-old volunteers (n = 32; P = 0.03 and P = 0.003, respectively). Catecholamine excretion was found to be significantly correlated with urine cortisol concentration (r = 0.54, P less than 0.05) and limb paresis (r = 0.52, P less than 0.05). In a multiple regression analysis, urine cortisol values were shown to be positively associated with limb paresis (P = 0.003), disorientation (P = 0.03) and body temperature (P = 0.03). High cortisol excretion was associated with a poorer functional outcome in a discriminant analysis (P = 0.001). Thus acute ischaemic stroke is associated with an increased activity in the cortisol axis. This may have a number of negative effects on organ functioning, and is a predictor of a poorer functional outcome.

Aged↗

PubMed1990

Pituitary-thyroid axis, prolactin and growth hormone in patients with acute stroke.

The pituitary-thyroid axis, serum prolactin and growth hormone levels were studied in 29 patients within 9 d of onset of acute ischaemic stroke. When compared to a control group of 80-year-old volunteers (n = 33), stroke patients were found to have elevated free thyroxine indices (P = 0.008), after adjustment for age and sex. Seventeen (81%) of the stroke patients showed a paradoxical rise in growth hormone in response to thyrotropin releasing hormone (TRH). In a multiple regression model, disorientation was associated with a low thyrotropin response to TRH (P = 0.02 and P = 0.04; 20 and 60 min after TRH, respectively). Disorientation was also positively correlated with the prolactin response to TRH (P = 0.045 after 60 min). Growth hormone levels were predicted by extensive motor impairment (P = 0.02). In conclusion, changes in pituitary and thyroid hormones were commonly observed after stroke and were closely associated with cognitive and/or motor impairment.

Aged↗

PubMed1990

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. The proportion of HLA-DR+ T cells was higher in CSF than PB in both MS and TH; this increase of DR+ T cells in CSF was more prominent in MS. The level of CD4+ CD8+ T cells, which represent a subset of activated T cells, was not different between CSF and PB, either in MS or in TH. The proportion of CD4- CD8- T cells, which were found generally not to be blast cells, was lower in CSF compared to PB in both patient groups. However, their CSF level was higher and their PB level lower in MS compared to TH. Results point to an accumulation of activated T-helper cells in the CSF of both MS patients and healthy subjects. Fetal-type CD4- CD8- T cells bearing the unusual T-cell receptor gamma/delta seem to be selectively recruited to the CSF of MS patients.

Adult↗

PubMed1990

Oestrogen treatment reduces duration of experimental allergic neuritis in rats and suppresses T cell responses to myelin.

The effects of oestrogen and pregnancy on the disease course of experimental allergic neuritis (EAN) in rats were investigated. Pregnant rats were totally protected from EAN and long term 17-beta-oestradiol treatment significantly shortened the disease duration. Lymph node cells from oestrogen treated rats had a suppressed proliferative response when stimulated with myelin or PPD, both when the response was measured immediately after cell preparation and after 72 h cell culture in vitro. Serum levels of IgG antibodies against myelin, P2 or PPD did not differ between treated and non-treated rats although oestrogen treated rats had significantly higher levels of total IgG. Immunohistochemical stainings of nerve roots showed less intensive invasion of T lymphocytes in the oestrogen treated group while immunoreactivity to both class I and II major histocompatibility complex antigens did not differ in between the groups. These findings show that oestrogen ameliorates EAN and suggest that this effect is mediated by suppression of T cell dependent immunity. Factors in addition to oestrogen may be operative during pregnancy when a total protection from EAN is obtained.

Animals↗

PubMed1990

Autoimmunity to collagen II and myelin basic protein: comparative studies in humans and rodents.

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Animals↗

PubMed1990

Autoreactive T lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma.

Multiple sclerosis (MS) is a disease with unknown cause characterized by inflammation and demyelination in the central nervous system. Although an autoimmune pathogenesis has been suggested, there are no conclusive data on the number of T cells autoreactive with myelin antigens in MS compared to controls. We showed that T lymphocytes secreting interferon-gamma in response to possible target autoantigens are severalfold more common among PBL mononuclear cells in patients with MS than in patients with aseptic meningitis and tension headache. On average T cells reactive with myelin basic protein (MBP), two different MBP peptides, or with proteolipid protein amounted to 2.7-5.2/10(5) PBL from MS patients. MBP-reactive T cells were still more frequent among mononuclear cells isolated from the cerebrospinal fluid (CSF; 185/10(5) CSF cells). We concluded that T cells reactive with myelin autoantigens are strongly increased in MS. This approach to detect them could allow definition of immunodominant T cell epitopes in individual MS patients, and thereby enable further development towards specific immunotherapy.

Adult↗

PubMed1989

Interferon-gamma-like immunoreactivity and T-cell marker expression in rat skeletal muscle fibres.

Interferon-gamma (IFN-gamma)-like-immunoreactivity was observed in subsets of rat skeletal muscle fibres with 3 different mouse monoclonal antibodies directed to rat IFN-gamma and a rabbit polyclonal anti-rat IFN-gamma-antibody. These strongly IFN-gamma-immunoreactive fibres also expressed antigen defining T-cells of the cytotoxic/suppressor phenotype (CD8) and major histocompatibility complex (MHC) class I antigen.

Animals↗