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Biomedical subjects

T Olsson

Publications and source records attributed to T Olsson.

At least 271 records · Page 15Linked to original sources
PubMed1992

Interactions between Trypanosoma brucei and CD8+ T cells.

The mechanisms for several important features o f African trypanosomiasis are still largely unexplained. These include (1) the occurrence of parasite growth-promoting molecules provided by the host, (2) polyclonal T- and B-cell activation and the development of immunosuppression and (3) neuropsychiatric signs. Here Tomas Olsson, Moiz Bakhiet and Krister Kristensson focus on interactive events between Trypanosoma brucei and CD8(+) T cells, and the release of a diffusible molecule from T. brucei that triggers CD8(+) T cells to produce interferon-gamma (IFN-gamma). This cytokine provides a growth stimulus for the parasite and modulates events in the host's immune and nervous systems.

Journal Article↗
PubMed1992

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. The beneficial effects of the drugs seem to be mediated primarily by an action on the autoimmune response, since in vitro lymphocyte proliferation in response to nervous tissue antigens was dose-dependently inhibited by both drugs, whereas the in vitro conductivity of demyelinated sciatic nerve was not significantly affected by the Ca++ antagonists. The suppressive effect on lymphocyte proliferation could partially be bypassed by protein kinase C activating phorbol ester alone or in combination with the Ca++ ionophore ionomycin, confirming a non-toxic effect of the Ca++ antagonists on lymphocytes.

Action Potentials↗
PubMed1992

Myelin antigen reactive T cells in cerebrovascular diseases.

T cell reactivities to the putative autoantigens myelin basic protein (MBP), MBP peptides with amino acid residues 110-128 and 148-165, and myelin proteolipid protein (PLP) were examined in patients with acute ischaemic cerebrovascular disease (CVD) and, for comparison, in patients with inflammatory neurological diseases and other neurological diseases. A quantitative measure of these T cell reactivities was obtained by assessing numbers of T cells among blood and cerebrospinal fluid (CSF) mononuclear cells that secreted IFN-gamma in response to antigen in vitro. Higher numbers of T cells reactive with each of these four antigens were detected in peripheral blood from patients with CVD compared with patients of the two control groups. Among blood cells from the CVD patients, their average number was 2.3-4.2/10(5) mononuclear cells. MBP reactive T cells were several-fold enriched in the CSF of CVD patients. The findings strongly suggest that brain damage in context with acute CVD leads to an in vivo expansion of myelin reactive T cells.

Adolescent↗
PubMed1992

The T-cell repertoire in myasthenia gravis involves multiple cholinergic receptor epitopes.

Antibodies against the alpha-subunit of the acetylcholine receptor (AChR) are found in most patients with myasthenia gravis and are considered to contribute to the receptor damage which leads to the characteristic signs and symptoms of the disease. This B-cell response is T-cell driven. Elevated T-cell reactivities to AChR and its alpha-subunit have been described in myasthenia gravis, and AChR alpha-subunit peptide reactive T-cell lines and clones preferentially recognizing certain defined sequence segments have been reported, thereby disclosing the possibility of specific immunotherapy. We have defined the T-cell repertoire to AChR, its alpha-subunit and the synthetic peptide sequences 100-117, 113-130, 143-163, 161-179, 207-225, 221-240, and 235-255 of the alpha-subunit in an immunospot assay which is based on secretion of interferon-gamma (IFN-gamma) by individual memory T cells upon stimulation with specific antigen in short-term cultures. Most patients with myasthenia gravis displayed T-cell reactivities to 1 to 6 different peptides. The mean numbers of T cells recognizing individual peptides varied in the myasthenia gravis patients between 1 per 77,000 and 1 per 167,000 peripheral blood mononuclear cells. None of the seven peptides evaluated could be identified as an immunodominant T-cell epitope, and any of them was found to dominate in individual patients. The numbers of T cells reacting with AChR and recombinant human AChR alpha-subunit were slightly higher (mean numbers 1 per 26,000 and 1 per 50,000 mononuclear cells, respectively). Such cells, as well as AChR alpha-subunit peptide reactive T cells, were also found in patients with other neurological diseases and in healthy subjects, but at lower frequencies and numbers. In myasthenia gravis, the elevated numbers of memory T cells recognizing multiple AChR alpha-subunit peptides may be crucial for the development of the disease, and the IFN-gamma released by such T cells might be important for its perpetuation.

Adolescent↗
PubMed1992

Abnormalities at different levels of the hypothalamic-pituitary-adrenocortical axis early after stroke.

BACKGROUND AND PURPOSE: Hypercortisolism is common in stroke patients. The aim of this study was to investigate possible disturbances at different sites within the hypothalamic-pituitary-adrenal axis. We also studied possible associations between hypercortisolism and clinical manifestations of brain dysfunction. METHODS: Patients with an acute ischemic stroke (n = 16; mean +/- SD age, 71 +/- 11 years) were compared with healthy elderly subjects (n = 9). We performed a short adrenocorticotropic hormone (ACTH) test with 0.25 mg 1-24 ACTH injected intravenously and an overnight dexamethasone suppression test with 1 mg dexamethasone given orally at 11 PM. RESULTS: Serum cortisol levels after dexamethasone at 8 AM were significantly higher in stroke patients (p = 0.003). The area under the curve for the cortisol response to ACTH was elevated in seven (47%) of stroke patients, and the centered cumulative cortisol response was elevated in three (20%) patients. The area under the curve response correlated significantly to the presence of an acute confusional state and male sex in stroke patients (rs = 0.63 and rs = 0.62, respectively; p < 0.05), whereas the centered cumulative cortisol response diminished with increasing age (rs = -0.62; p < 0.05). Postdexamethasone cortisol levels were significantly correlated to the presence of an acute confusional state and to extensive limb paresis (rs = 0.66 and rs = 0.62, respectively; p < 0.05). CONCLUSIONS: There are abnormalities in the cortisol axis both at the central level and at the adrenal level early after stroke. Hypercortisolism is closely associated with cognitive disturbances and extensive motor impairment.

Adrenal Cortex↗
PubMed1992

Conjugal multiple sclerosis: immunogenetic characterization and analysis of T- and B-cell reactivity to myelin proteins.

We describe two families with conjugal multiple sclerosis. Onset of symptoms in the husbands occurred 11 and 17 years after onset of relapsing/remitting symptoms in their wives. There were no similarities regarding clinical manifestations of MS within each family. Evaluation of T-cell repertoire by enumeration of cells secreting interferon-gamma in response to proteolipid protein (PLP), myelin basic protein (MBP), and to various synthetic MBP peptides revealed similar patterns of T-cell reactivity within the families both in MS-affected parents and unaffected children. Genomic HLA-DR-DQ typing showed that T-cell reactivity was independent of HLA class II phenotype. Analysis of B-cell responses in blood showed low numbers of cells secreting IgG, IgA, or IgM antibodies against MBP, PLP, myelin-associated glycoprotein, and myelin-oligodendrocyte glycoprotein both in MS-affected and unaffected family members. In conclusion, our study of two families with conjugal MS has shown a dominant T-cell response against the same MBP peptide within the family both in MS-affected parents and unaffected children, and this T-cell response seems to be independent of the HLA class II phenotypes of the family members.

Adult↗
PubMed1992

Facial nerve transection causes expansion of myelin autoreactive T cells in regional lymph nodes and T cell homing to the facial nucleus.

Nervous tissue expression of immunological signal and recognition molecules, as well as lymphoid tissue immune responses after facial nerve trauma was studied in male rats of the Lewis and Brown Norway (BN) strains. In both rat strains nerve transection caused within four days the appearance of IFN-gamma-like immunoreactivity in the cytoplasm of axotomized motor neurons and an induction of MHC class I and II, and CD4 molecules on surrounding glial cells to a similar extent. T lymphocytes also infiltrated the facial nuclei ipsilateral to the axotomy in all animals. The number of autoreactive T cells in superficial cervical lymph nodes, which in response to whole myelin or peptides of myelin basic protein (MBP) secreted IFN-gamma increased markedly after axotomy. This response was more conspicuous in Lewis rats, which are susceptible to experimental allergic encephalomyelitis (EAE), than in BN rats, which are EAE resistant. A proportion of the axotomized Lewis rats also developed widespread perivascular infiltration of mononuclear cells in the CNS, reminiscent of EAE. Hypothetically, a strong expansion of myelin autoreactive IFN-gamma producing T cells secondary to nerve trauma may have immunopathological consequences in genetically predisposed individuals. It is also possible that myelin reactive T cells, whether recruited to the lesioned nerve, could have impact on macrophage function during Wallerian degeneration in the distal stump.

Animals↗
PubMed1992

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. In contrast, the drug caused a decrease of proliferation of cells stimulated with PHA. The number of cells induced to IFN-gamma secretion was reduced by SITS. The suppressive effect was dependent on the degree of activity of cells without drugs. Cultures showing high numbers of BPM reactive T cells were more easily suppressed than cultures with low numbers of BPM reactive T cells. Our results suggest that anion channel gating is involved in the triggering of T cells to IFN-gamma secretion. The anion channel signal pathway in lymphocytes could be a target for pharmacological intervention in inflammatory disorders. In the presently used autoimmune model, EAN, the net effect of in vivo treatment with SITS resulted in worsening of clinical signs and increased inflammatory cell infiltration in sciatic nerve, whereas the in vitro conductivity of sciatic nerve was not significantly affected by the drug. Thus anion channel gating seems to regulate activities of immune cells, and drugs with anion channel blocking properties may have effects that enhance autoimmune disease.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

Immunology of multiple sclerosis.

Recent advances in the understanding of the immunology of multiple sclerosis (MS) are discussed. In the central nervous system (CNS) major histocompatibility complex (MHC) class I and II antigens, and lymphocyte adhesion molecules are expressed. Furthermore, there are cells present which produce important effector molecules such as interferon (IFN)-gamma and tumor necrosis factor (TNF). A role for myelin antigen-specific autoimmunity is supported, but not proven, by the presence of a marked quantitative increase of T and B cells with such specificities, enriched to the CNS. Several myelin antigens, as well as a multitude of peptide parts of these, are apparently recognized. It will be of interest to study the functional abilities of these cells and how they are regulated.

Autoimmune Diseases↗
PubMed1991

Assessment of the inhibitory effect of immunosuppressive agents on rat T cell interferon-gamma production using an ELISPOT assay.

The immunospot (ELISPOT) assay has proven to be an efficient and sensitive method for the enumeration of single cells secreting antibodies or cytokines. Here we show that the generation of interferon-gamma producing cells (IFN-gamma pc) in rat spleen cell cultures stimulated with concanavalin A (ConA) is dose-dependently inhibited by a wide variety of immunosuppressants such as cyclosporin A, FK506, hydrocortisone, dexamethasone, azathioprine and ART-18, a monoclonal antibody (mAb) with established immunosuppressive activity in organ transplantation and autoimmunity. The minimal inhibitory concentration (m.i.c.) correlated well with the reported m.i.c. in the mixed lymphocyte reaction (MLR) assay and the therapeutically effective plasma levels in vivo. Our data indicate that the IFN-gamma-specific immunospot assay is a powerful tool for determining the potency of immunosuppressive agents in vitro and provides a simple and accurate method for screening large numbers of agents with suspected immunosuppressive properties. The assay may additionally prove to be of value for determining the therapeutically effective doses of immunosuppressants that should be administered in vivo.

Animals↗
PubMed1991

Serum dehydroepiandrosterone sulfate in Alzheimer's disease and in multi-infarct dementia.

Circulating levels of dehydroepiandrosterone sulfate (DHEAS) and cortisol were studied in 86 patients with dementia; 45 with Alzheimer's disease and 41 with multi-infarct dementia. Compared to an elderly control group, after adjustment for age and sex, patients with Alzheimer's disease were found to have lower serum levels of DHEAS. We found a covariation between serum albumin and DHEAS levels, which may be of importance regarding peripheral hormone concentration in patients with dementia. These findings may provide evidence for a role of DHEAS in amnestic disorder in humans, either reflecting or contributing to the course of dementing diseases.

Aged↗
PubMed1991

T and B cell responses to myelin-oligodendrocyte glycoprotein in multiple sclerosis.

The pathogenesis of multiple sclerosis (MS) is believed to involve an autoimmune component directed against the myelin sheath. One potential target Ag for such autoimmune attack is the myelin-oligodendrocyte glycoprotein (MOG) because an anti-MOG mAb has profound influence on the course of experimental autoimmune encephalomyelitis, which to some extent represents an experimental model of MS. Using single cell assays, we have evaluated T and B cell reactivities to MOG in MS patients and controls. T cell reactivity was estimated by counting the number of cells that secreted IFN-gamma in response to MOG, whereas B cell reactivity was estimated by enumerating cells secreting antibodies that bound to MOG. MOG reactive T cells were detected in the peripheral blood of the majority of the 16 MS patients examined (mean 1/7299 mononuclear cells), but infrequently and at lower numbers in samples from neurologic controls. MOG-reactive T cells were more frequent among MS patients' cerebrospinal fluid (CSF) mononuclear cells (mean 1/450 cells). The T cell response to MOG was evidently MHC class II restricted, because Fab fragments of a rabbit polyclonal anti HLA-DR antibodies abrogated the Ag-induced increase in number of cells that secreted IFN-gamma, as analyzed on CSF and PBMC from three patients with MS. Anti-MOG IgG antibody-secreting cells were detected in blood in 8 of 16 MS patients (mean 1/25,641 cells), but they were also strongly accumulated in CSF, being detected in 8 of 10 MS patients examined (mean 1/265 cells), while rarely found in controls. The findings imply that MOG may represent a pathogenetically important target Ag in MS.

Adult↗
PubMed1991

Antibodies to myelin-associated glycoprotein are found in cerebrospinal fluid in polyneuropathy associated with monoclonal serum IgM.

Antibodies to myelin-associated glycoprotein (MAG) have been demonstrated in the serum samples from about half the patients with polyneuropathy associated with serum IgM monoclonal component. We examined cerebrospinal fluid (CSF) and serum samples from 13 patients with this disease by enzyme-linked immunosorbent assay for anti-MAG IgM antibodies. We detected these antibodies in both CSF and serum samples in 10 of the patients; in three of them the antibodies were at higher levels in the CSF. The remaining three patients had anti-MAG IgM antibodies in the CSF only. Intrathecal production of anti-MAG IgM antibodies is thus common in polyneuropathy associated with IgM monoclonal component. In three patients, examined on two occasions from 1 to 7 years, high anti-MAG IgM antibody levels persisted in CSF and serum samples. Among 165 patients with other neurologic diseases, including 60 with multiple sclerosis and 60 control subjects with tension headache, anti-MAG IgM antibodies were detected in the CSF from three patients (two with multiple sclerosis, one with aseptic meningitis), and in the serum sample of one patient with multiple sclerosis. Whether the frequent occurrence of anti-MAG IgM antibodies in CSF and their intrathecal synthesis has pathogenetic relevance for the development of polyneuropathy associated with IgM monoclonal component is unsure.

Aged↗
PubMed1991

Chronic experimental autoimmune encephalomyelitis induced by the 89-101 myelin basic protein peptide in B10RIII (H-2r) mice.

Development of experimental allergic encephalomyelitis (EAE) in the SJL (H-2s) mice is associated with a T cell-dependent autoimmune response to the C-terminal part of the myelin basic protein (MBP). In this study the influence of both H-2 and non-H-2 genetic background on EAE induced with the MBP89-101 peptide is described. Analysis of different H-2q haplotype strains, B10G, B10Q, SWR and NFR/N, showed that the B10 background is relatively resistant to disease induction. Both SWR and NFR/N were susceptible to EAE showing that the H-2q haplotype is permissive for EAE development induced with MBP89-101 and that the T cell receptor (TcR) haplotype or complement C5 deficiency exert no significant influence on disease susceptibility. In a series of H-2-congenic strains on the B10 background only B10RIII (H-2r) mice were susceptible to EAE. The B10RIII mice developed a severe EAE with early onset and chronic progressive or relapsing course of disease. In addition, B10RIII mice treated with Freund's complete adjuvant and pertussis toxin alone showed an early monophasic disease. The clinical observations were confirmed by immunohistopathologic analysis of the central nervous system. In these studies, we also applied antibodies to different TcR V beta elements which showed no specific limitation of the used TcR among infiltrating T cells in the target tissue in any of the strains. It is concluded that an MBP peptide-specific disease can be induced in three different haplotypes and it is possible that shared structures between the As, Aq and Ar molecules are of importance for the trigger of encephalitogenic T cells with different TcR V elements. The presently described chronic EAE model induced in the B10RIII mice will be of value as a model for multiple sclerosis.

Adjuvants, Immunologic↗