Biomedical subjects

T Olsson

Publications and source records attributed to T Olsson.

At least 289 records · Page 16Linked to original sources

PubMed1991

Autoreactive T and B cells responding to myelin proteolipid protein in multiple sclerosis and controls.

The pathogenesis of multiple sclerosis (MS) could involve an autoimmune response to proteolipid protein (PLP). Immunization of experimental animals with this major myelin protein can lead to experimental allergic encephalomyelitis. To identify a possible role of PLP as target antigen in MS, we evaluated T cell immunity to PLP in blood and cerebrospinal fluid (CSF) from patients with MS and controls by counting cells which in response to PLP in short-term cultures secreted interferon-gamma. The PLP-specific B cell response was analyzed by counting cells secreting anti-PLP antibodies. PLP-reactive T cells were detected in blood of most MS patients (mean value 1 per 20,408 mononuclear cells), and at 41-fold higher numbers in CSF (mean 1 per 500 CSF cells). Anti-PLP IgG antibody-secreting cells were detected in blood from most MS patients (mean 1 per 30,303 cells), but such cells were 49-fold more frequent in CSF (mean 1 per 625 cells). PLP-reactive T and B cells were also detected in blood and CSF from control patients, but at much lower numbers. A strong and persistent autoimmune response to PLP as well as to other myelin proteins, enriched in CSF, is proposed to be pathogenetically important in MS.

Adolescent↗

PubMed1991

Bidirectional activating signals between Trypanosoma brucei and CD8+ T cells: a trypanosome-released factor triggers interferon-gamma production that stimulates parasite growth.

The hemoflagellate Trypanosoma brucei (T.b.) is the cause of African sleeping sickness. T. b. brucei which is pathogenic for rodents but nonpathogenic for humans was used to examine the interactions between the parasite and mononuclear cells (MNC). Co-cultivation in vitro of rat or human MNC and T.b. brucei resulted in a rapid non-antigen-specific release of interferon-gamma (IFN-gamma) which was dependent on CD8+ lymphoid cells. The parasites triggered MNC proliferation if IFN-gamma was blocked by a specific antibody in vitro. Separate cultures of parasites and MNC in a two-chamber system allowing exchange of soluble mediators showed CD8+ cell-dependent MNC triggering, indicating that a diffusable factor released by trypanosomes acts on the MNC. Gel filtration according to molecular mass of disrupted parasites and assay of the fractions revealed a peak activity at an approximate molecular mass of 185 kDa for the trypanosome-derived lymphocyte-triggering factor (TLTF). Conversely, there was a CD8+ cell-dependent action of MNC on the trypanosomes. MNC released a diffusable factor that in short-term experiments caused a striking increase in number of parasites. This effect was inhibited by antibodies against rat IFN-gamma. The increase in number of trypanosomes was promoted by rat MNC or rat IFN-gamma but not human MNC or human IFN-gamma suggesting a species-restricted recognition of IFN-gamma. An in vivo uptake of IFN-gamma by the parasites was suggested by immunohistochemical staining of T.b. brucei with an mAb against rat IFN-gamma and Western blot of the parasites showing a band with a molecular mass corresponding to IFN-gamma. The bidirectional signals we define here may explain certain features of trypanosomiasis, i.e. T cell activation, immunosuppression and host-range restriction. The seemingly important role of the TLTF indicates that it should be purified and explored as target for immune-specific intervention.

Animals↗

PubMed1991

Cells producing antibodies specific for myelin basic protein region 70-89 are predominant in cerebrospinal fluid from patients with multiple sclerosis.

Cells secreting antibodies against guinea pig myelin and synthetic myelin basic protein (MBP) peptides were evaluated in cerebrospinal fluid (CSF) and blood from patients with multiple sclerosis (MS) and a variety of other neurological diseases (OND). The peptides used, reproducing amino acid sequences 1-20, 70-89, 108-126, or 157-166 of MBP, were selected on the basis of their hydrophilic and encephalitogenic properties. Low numbers of cells secreting IgG antibodies against myelin or each of the MBP peptides (about 1 per 50,000) were detected in peripheral blood, with no difference between MS and OND. In CSF, cells secreting IgG antibodies to MBP 70-89 were more frequently (p = 0.007) detected in patients with MS (1/380 IgG-secreting cells on average) than in patients with OND (1/2083 IgG-secreting cells on average). The frequencies of cells secreting antibodies against myelin or the three other MBP peptides were similar in MS and OND. Thus, evaluation of B cell immunity at the cellular level indicates that MBP 70-89 is an immunodominant B cell epitope in MS. It is not clear whether this intrathecal anti-MBP 70-89 IgG antibody response has any pathogenetic relevance in MS or is the result of myelin breakdown.

Adult↗

PubMed1991

Interferon-gamma-like immunoreactivity in developing rat spinal ganglia neurons in vivo and in vitro.

Interferon-gamma-like immunoreactivity was observed in a subpopulation of 16-day-old embryonic rat spinal ganglion neurons using two monoclonal antibodies directed against different epitopes of recombinant interferon-gamma. During ontogenesis both in vivo and in vitro, it was found that the strong immunoreactivity was confined to small neurons when neurons become morphologically distinct on the basis of size. In vivo, the interferon-gamma-immunoreactive neurons started to express major histocompatibility complex class I antigens after the first postnatal week, while in vitro no such antigen could be detected. A quantitative Elisa method was developed to determine the levels of major histocompatibility complex class I and interferon-gamma in vitro, whereby increased amounts of major histocompatibility complex class I antigen was detected after exposing the cultures to recombinant interferon-gamma and Sendai virus. Sendai virus also caused a small increase in interferon-gamma with a peak about 12 hours after infection. The in vitro system will be used to study further the role of the putative neuronal interferon-gamma-like molecule in the regulation of cell growth, for induction of major histocompatibility complex antigens and in virus infection of sensory neurons.

Animals↗

PubMed1991

Catecholamine excretion in old age.

Catecholamine excretion was studied in two groups of nonhospitalized subjects, 60 and 80 years of age, N = 35 and 29, respectively. Urinary 24h dopamine excretion exhibited an age-related decline (p = 0.001). There was a sex difference for dopamine excretion; men had higher excretion levels (p = 0.04). Twenty-four-hour excretion of epinephrine and norepinephrine was slightly higher in 60- than in 80-year-old individuals (NS). Smoking was associated with a considerable increase in epinephrine (p = 0.001) and norepinephrine (p = 0.04) excretion. Body mass index was negatively correlated to epinephrine excretion (r = -0.27; p less than 0.05). When analyzed with a multi-way analysis of variance with analysis of covariance, significant influences of age on dopamine excretion, of creatinine clearance on dopamine and norepinephrine excretion, and of smoking on epinephrine excretion were seen. Thus, factors such as age, gender, body mass, kidney function and smoking habits considerably influence catecholamine excretion in elderly people.

Aged↗

PubMed1991

Mast cells in brains during experimental allergic encephalomyelitis in Lewis rats.

We studied the number of mast cells and their extent of degranulation in brains of Lewis rats with acute experimental allergic encephalomyelitis (EAE), activity induced with guinea pig spinal cord and Freund's complete adjuvant. Non-immunized controls and EAE rats were killed on days 10, 11, 12, and 16 post-immunization (p.i.). The percentage of degranulated mast cells was significantly increased in EAE brains. Signs of degranulation were observed as early as day 10 p.i. Clinical EAE signs appeared from day 10 p.i. A significant change in mast cell number was not observed. The percentage of degranulated cells was largest at day 16 p.i., at a time when the inflammation had reached the thalamus. This indicates that mast cell degranulation may occur as a result of the inflammation. Collectively, the data suggest that mast cells may play a role in the pathogenesis of EAE.

Animals↗

PubMed1991

A monoclonal antibody against HSV type 1 ribonucleotide reductase cross-reacts with the P0 protein of peripheral nerve myelin.

An epitope on peripheral nerve myelin was detected by the use of a mouse monoclonal antibody directed against the 38 kDa subunit of herpes simplex virus (HSV) type 1 ribonucleotide reductase. Immunohistochemistry showed reactivity solely in PNS myelin. In nerve roots there was a sharp border in transitional zones to the negative CNS myelin. The immunoreactivity was found in rat, guinea pig, bovine and human peripheral nerves. Western blot analysis of peripheral nerve myelin as well as purified P0 revealed a distinctly stained band corresponding to a molecular weight of approximately 29 kDa. The present finding of a shared antigenic determinant between HSV ribonucleotide reductase and peripheral nerve P0 may be of pathogenetic relevance in virus induced demyelinating diseases in the peripheral nervous system.

Animals↗

PubMed1991

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. There was a positive correlation between CD4-8- T cells and T cell receptor (TCR) gamma delta bearing T cells in blood and CSF. The double-negative T cells exceeded the TCR gamma delta T cells by about 1%. A positive correlation between CD5+ B cells and CD4-8- T cell level in CSF was found in MS and AM, but not in TH, nor in blood of any patient group. HLA-DR expression was lower in CD5+ B cells than in CD5- B cells. We conclude that fetal-type lymphocytes are enriched in CSF compartment of patients with inflammatory diseases of the central nervous system, irrespective of autoimmune mechanisms involved, but the function of CD5+ B cells is mainly to produce the autoantibodies.

Adolescent↗

PubMed1991

T cell immunity and interferon-gamma secretion during experimental allergic encephalomyelitis in Lewis rats.

An immunospot assay that detects single secretory cells was used to enumerate interferon-gamma secreting cells (IFN-gamma-sc) in mononuclear cell suspensions from the central nervous system (CNS) and peripheral lymphoid organs after actively induced experimental allergic encephalomyelitis (EAE) in Lewis rats. In the CNS compartment there was a significant increase in the number of IFN-gamma-sc preceding the onset of the clinical signs of EAE. Both in rats with EAE and rats immunized with Freund's complete adjuvant (FCA) the number of IFN-gamma-sc increased in peripheral lymphoid organs, as compared to non-immunized controls. In view of the potent immunoregulatory effects of IFN-gamma, its intra-CNS secretion may play a crucial role for clinicopathological events in EAE. To study the numbers of primed T cells that in response to myelin antigens produced IFN-gamma, mononuclear cell suspensions from peripheral lymphoid organs were precultured to allow for antigen uptake, presentation and T cell triggering, followed by enumeration of IFN-gamma-sc. T cells responding to a peptide of myelin basic protein (MBP) that previously have been shown encephalitogenic in Lewis rats, appeared initially and were quantitatively dominant over the course of EAE. Later, T cell reactivities to multiple regions of MBP appeared, showing that the concept of immunodominance in EAE is non-absolute and time dependent. Splenocyte cultures from EAE rats exposed to the different antigens showed a reduced number of IFN-gamma-sc compared to cultures not exposed to antigen, suggesting an antigen-induced suppression of T cell effector molecules.

Animals↗

PubMed1991

Gamma interferon expression and major histocompatibility complex induction during measles and vesicular stomatitis virus infections of the brain.

Lymphocytic interferon gamma (IFN-gamma) production and major histocompatibility complex (MHC) antigen induction were studied in experimental measles and vesicular stomatitis virus infections in the brain. Fifteen-day-old Sprague-Dawley rats injected intracerebrally with the HNT strain of measles virus showed already within 1 day after infection an increased number of cells producing IFN-gamma in the spleen, cervical lymph nodes and leptomeninges. These rats recovered after a transient neuronal infection in the brain. Rats infected intracerebrally with vesicular stomatitis virus, on the other hand, all succumbed after 2 days and showed no IFN-gamma production in lymphoid cells. Immunohistochemically MHC class I antigen appeared in infected and uninfected cells in the brain during replication of both viruses. A role for the recently discovered nerve fibres with IFN-gamma-like immunoreactivity, which are normally present in the brain, in the MHC antigen induction is discussed.

Animals↗

PubMed1991

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.i.). All doses led to a clinically more protracted disease, increased numbers of T cells infiltrating into the central nervous system (CNS) and to increased numbers of interferon-gamma-secreting cells (IFN-gamma-sc) in the CNS. The effects of SASP treatment on T cell-mediated autoimmunity against CNS myelin and peptides of myelin basic protein (MBP) were measured by IFN-gamma secretion and proliferation by lymph node mononuclear cells in response to these antigens. In SASP-treated rats, increased numbers of IFN-gamma-sc appeared in response to myelin antigens, while the proliferative responses were decreased. We suggest that monitoring cell-mediated immunity with the IFN-gamma-sc method may be relevant for the evaluation of new immunotherapeutic strategies in inflammatory demyelinating diseases. Furthermore, our results demand caution as to clinical trials with SASP in MS.

Animals↗

PubMed1991

Cells secreting anti-MAG antibody occur in cerebrospinal fluid and bone marrow in patients with polyneuropathy associated with M component.

Occurrence and distribution of cells secreting antibodies against myelin associated glycoprotein (MAG) were studied in 9 patients with polyneuropathy associated with the monoclonal (M) component in serum. Utilizing an immunospot assay, we found that 4 of 7 patients with polyneuropathy associated with an IgM M component had cells secreting anti-MAG IgM antibody in cerebrospinal fluid (CSF) numbering between 1 per 212 and 1 per 3333 mononuclear cells. All 7 patients had cells secreting anti-MAG IgM antibody in bone marrow (median value 1 per 2000 cells). In contrast, peripheral blood from only 2 of these patients contained low numbers of such cells. One patient with polyneuropathy associated with an IgA M component had cells secreting anti-MAG IgA antibody in CSF, and 1 with an IgG M component had cells secreting anti-MAG IgG antibody in CSF; both patients also had anti-MAG IgM antibodies detectable in CSF only by ELISA. These 2 patients may thus have concurrent intrathecal production of antibodies of 2 different isotypes which are directed against the same or different epitopes of MAG. The production of antibodies directed against a component of myelin occurring in the immediate vicinity of the peripheral nervous system might be involved in the pathogenesis of the polyneuropathy.

Adult↗

PubMed1991

Assessment of hypothalamic-pituitary function in patients with familial amyloidotic polyneuropathy.

This study was performed to evaluate hypothalamic-pituitary hormone regulation in patients with familial amyloidotic polyneuropathy. Twenty-two patients without clinically overt endocrinological dysfunction were studied. A thyrotropin-releasing hormone test revealed abnormal growth hormone regulation in 9 of 17 (53%) patients, and abnormal prolactin regulation in 9 of 18 (50%) patients. Abnormalities in either growth hormone or prolactin regulation were found in 12 of 17 (71%) patients. Serum somatomedin C levels were normal in all 22 patients. In 3 of 18 (17%) patients the plasma arginine vasopressin levels were low relative to the serum osmolality levels. Thus abnormalities in hypothalamic-pituitary hormone regulation may be common in familial amyloidotic polyneuropathy.

Amyloidosis↗

PubMed1991

Multiple sclerosis: cells secreting antibodies against myelin-associated glycoprotein are present in cerebrospinal fluid.

We evaluated the B-cell response in cerebrospinal fluid (CSF) and blood by enumerating cells secreting antibodies to myelin-associated glycoprotein (MAG) and, for reference, to myelin basic protein (MBP), two myelin components which may constitute targets for autoimmune attack in multiple sclerosis (MS). Among 25 untreated MS patients, 12 had cells in CSF secreting anti-MAG IgG antibodies (mean value 1 per 1429 CSF cells) and three also had cells secreting anti-MAG antibodies of the IgM isotype but at lower levels. In CSF from 2 out of 10 MS patients examined, anti-MAG and anti-MBP IgG antibody-secreting cells were present concurrently. Antibody-secreting cells were less frequent in blood and bone marrow, reflecting compartmentalization to CSF. Anti-MAG antibody-secreting cells were found in CSF from only 1 out of 27 control patients. The intrathecal production of anti-MAG and anti-MBP antibodies may be important in the pathogenesis of MS.

Adult↗

PubMed1991

Anti-Borrelia burgdorferi antibody response over the course of Lyme neuroborreliosis.

Characteristic findings on examination of cerebrospinal fluid (CSF) in Lyme neuroborreliosis include mononuclear pleocytosis, oligoclonal immunoglobulin G (IgG) bands, and evidence for local production of specific antibodies. We utilized an immunospot assay to detect cells secreting anti-Borrelia burgdorferi antibodies of different isotypes over the course of disease. Such cells were detected in CSF from 13 consecutive patients with neuroborreliosis examined before treatment. IgG antibody-secreting cells were present in high numbers (mean, 32 cells per 10(4) CSF cells), whereas IgA and IgM antibody-secreting cells were found less frequently and at lower numbers (mean, 5 and 6 cells per 10(4) CSF cells, respectively). Clinical improvement after penicillin treatment was paralleled by a rapid decline of antibody-secreting cells in CSF, but they were still detected, although at lower numbers, in 5 of 10 patients examined more than 6 months after treatment. This specific B-cell response persisted despite clinical improvement. Whether it reflects persistence of antigen is unsettled.

Adult↗

PubMed1991

Origin of cardiac-related thoracic electrical impedance variations in lambs.

Cardiac-related deflections in thoracic electrical impedance have been thought to correlate sufficiently well with cardiac stroke volume to be used as the basis for a noninvasive estimation of cardiac output. To determine more precisely the physiological origin of the impedance deflection (DZ), we regarded right ventricular stroke volume (SVa) as the sum of two components: 1) that part of SVa responsible for the transient increment in pulmonary blood volume within a cardiac cycle, SVa-v and 2) the remaining part of SVa, (SVa-SVa-v). SVa-v was measured in lambs by integration of the difference between pulmonary arterial and pulmonary venous flow. SVa and its components were varied experimentally by opening and closing an aorticocaval shunt or by inflating and deflating a cuff implanted around the pulmonary artery. DZ was measured using a tetrapolar disk electrode system. Multivariate linear regression analysis revealed that SVa-v had a significant positive effect on DZ, and, at the same time, (SVa-SVa-v) had a significant negative effect on DZ. In the pulmonary artery occluder model, the positive effect of SVa-v dominated the opposing negative effect of (SVa - SVa-v) so that the net effect of SVa on DZ was positive and significant. In the aorticocaval shunt model, these effects opposed each other to the extent that there was no significant correlation between SVa and DZ. These results shed new light on the physiological origin of DZ. They also demonstrate that use of DZ to measure acute changes in cardiac output may yield misleading results. Changes or the lack of changes in thoracic electrical impedance do not necessarily reflect cardiac output status.

Animals↗

PubMed1991

Acetylcholine receptor-reactive T and B cells in myasthenia gravis and controls.

Myasthenia gravis (MG) is strongly associated with antibodies to acetylcholine receptor (AChR), whereas the extent of T cell involvement is not settled. The number of cells secreting interferon-gamma (IFN-gamma) in response to AChR during 48 h culture of blood mononuclear cells (PBL) may reflect AChR-reactive T cells. Using an immunospot assay, we detected such cells in 23 of 30 patients with MG at a mean number of 1 per 33.333 PBL. AChR-reactive T cells were also found in patients with other neurological diseases (OND) and in healthy subjects but at lower frequencies and numbers. The T cell response to purified protein derivative and to PHA, and also to two major myelin proteins (basic protein and proteolipid protein) did not differ between MG and the two control groups, underlining the specificity of an augmented T cell reactivity to AChR in MG. Evaluation of the B cell response by enumerating anti-AChR IgG antibody secreting cells revealed such cells in 27 of 28 patients with MG at a mean value of 1 per 14,085 PBL. Cells secreting anti-AChR antibodies of the IgA and IgM isotypes were also detected in MG, but less frequently, at lower numbers, and only in conjunction with IgG antibody secreting cells. Anti-AChR antibody secreting cells were also found among patient with OND and in healthy controls, but at lower frequencies and numbers. These data confirm that AChR is a major target for autoimmune response in MG.

B-Lymphocytes↗

PubMed1991

Cells secreting antibodies to myelin basic protein in cerebrospinal fluid of patients with Lyme neuroborreliosis.

An autoimmune response to myelin basic protein (MBP) has been proposed to participate in the development of the chronic neurologic manifestations that may accompany Borrelia burgdorferi-induced Lyme disease. Using an immunospot assay, we counted cells secreting antibodies to MBP. Anti-MBP IgG antibody-secreting cells were detected in CSF from eight of 13 consecutive patients with Lyme neuroborreliosis irrespective of stage of disease. The numbers were between 1/370 and 1/5,000 CSF cells (mean, 1/1,250 in the 13 patients). The highest numbers were encountered in two patients with severe signs of CNS involvement. The numbers decreased in parallel with clinical improvement after treatment. Anti-MBP IgG antibody-secreting cells were also observed in the CSF from patients with a variety of other inflammatory diseases of the nervous system, and their role in the development of tissue damage remains unsettled. Anti-MBP IgG antibody-secreting cells were not detected in the patients' blood, reflecting accumulation of this autoantibody response to CSF.

Adult↗