PubMed Health⌕ Search

Biomedical subjects

T Olsson

Publications and source records attributed to T Olsson.

At least 19 recordsLinked to original sources
PubMed1995

Increased mRNA expression of IL-6, IL-10, TNF-alpha, and perforin in blood mononuclear cells in human HIV infection.

Evidence has been presented for the involvement of various cytokines, including interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha, in the pathogenesis of human immunodeficiency virus (HIV) infection. Since measured plasma levels may poorly reflect in vivo production of cytokines, we adopted in situ hybridization with cDNA oligonucleotide probes to enumerate blood mononuclear cells (MNCs) expressing mRNA for IL-6, IL-10, TNF-alpha, and perforin. The HIV-infected patients had elevated levels of MNCs expressing mRNA for all four cytokines compared to healthy controls. Numbers of IL-6 mRNA-expressing cells were higher in patients with clinical AIDS than in asymptomatic seropositive patients, and correlated inversely with CD4+ cell counts in blood, reflecting the involvement of IL-6 in later stages of HIV infection. The described approach could be an alternative way to study cytokines in HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Transcription factor AP-2 gene expression in adult rat hippocampal regions: effects of environmental manipulations.

Environmental enrichment increases glucocorticoid receptor expression in hippocampal pyramidal neurons, but the molecular mechanisms are unknown. Several transcription factors are expressed in hippocampal neurons where they respond to environmental stimuli. In this study 12 adult male rats (n = 6 in each group) were exposed to enriched or isolated environment for 30 days. The expression of AP-2 mRNA, studied by in situ hybridization, was attenuated by environmental enrichment in the CA2 and CA3 subfields of the hippocampus. AP-2 may be involved in the environmental effect of glucocorticoid receptor gene expression in these neurons.

Animals↗
PubMed1995

Interferon gamma, interleukin 4 and transforming growth factor beta in experimental autoimmune encephalomyelitis in Lewis rats: dynamics of cellular mRNA expression in the central nervous system and lymphoid cells.

The potential role of certain important immunoregulatory and effector cytokines in autoimmune neuroinflammation have been studied. We have examined the expression of mRNA, with in situ hybridization, of interferon gamma (IFN-gamma), interleukin 4 (IL-4) and transforming growth factor beta (TGF-beta) both in sections of spinal cords and the antigen-induced expression of these cytokines by lymphoid cells after stimulation with a dominant encephalitogenic peptide of MBP (MBP 63-88) during the course of actively induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats. In spinal cords, the target organ in EAE, cells expressing mRNA for IFN-gamma, first appeared at the onset of clinical signs, i.e., day 10 postimmunization (p.i.), peaked at the height of disease (day 13 p.i.) and then gradually decreased concomitant with recovery. Very few IL-4 mRNA-expressing cells appeared in the spinal cord with no clear relation to clinical signs or histopathology. In contrast, expression of mRNA for TGF-beta did not increase until day 13 p.i., at height of the disease, shortly preceding recovery. These data are consistent with a disease upregulating role of IFN-gamma, while TGF-beta may act to limit central nervous system (CNS) inflammation. In lymphoid organs, primed MBP 63-88 reactive T cells showed an interesting time-dependent evolution of their cytokine production in vitro. Thus, early after immunization there was a conspicuous MBP 63-88-induced production of both IFN-gamma and IL-4. Such cells may act in the initiation and promotion of the disease. Later, in the recovery phase, MBP 63-88 induced lymphoid cells to TGF-beta production. Thus, an autoantigen-specific production of TGF-beta occurred during EAE and hypothetically such a mechanism may serve to downregulate aggressive autoimmunity systemically.

Amino Acid Sequence↗
PubMed1995

Depletion of CD8+ T cells suppresses the development of experimental autoimmune myasthenia gravis in Lewis rats.

To understand the role of CD8+ T cells in experimental autoimmune myasthenia gravis (EAMG), CD8+ T cells were depleted by injecting a monoclonal anti-rat CD8 antibody (OX8) into Lewis rats immunized with Torpedo acetylcholine receptor (AChR) in complete Freund's adjuvant (CFA). CD8-depleted EAMG rats showed strikingly less muscle weakness and lower anti-AChR IgG antibody levels compared to Hy2-15-injected control EAMG rats. Moreover, the numbers of AChR-specific IgG antibody-secreting cells, AChR-reactive interferon-gamma-secreting T helper type 1-like cells and lymphocyte proliferation to AChR were lower in the CD8-depleted group than in control EAMG rats. These differences were significant among mononuclear cells from inguinal and popliteal lymph nodes, mesenteric lymph nodes and spleen, but not from thymus when examined 3, 5 and 7 weeks post-immunization. We suggest that CD8+ T cells are involved in the induction and persistance of EAMG by directly or indirectly affecting AChR-reactive T cells and anti-AChR IgG antibody-secreting cells.

Animals↗
PubMed1995

Spreading of the immune response to different myelin basic protein peptides in chronic experimental autoimmune encephalomyelitis in B10.RIII mice.

B10.RIII mice develop chronic and relapsing experimental autoimmune encephalomyelitis (EAE) after immunization with the myelin basic protein (MBP) peptide 89-101 (VHFFKNIVTPRTP). To investigate the basis for the chronicity of the disease, the subsequent development of an immune responses to other parts of the MBP protein were investigated. Onset of disease occurs 9-25 days after immunization with MBP89-101. T cell responses towards a series of MBP peptides were assessed in an enzyme-linked immunospot assay detecting single cells secreting IFN-gamma. There were responses not only to MBP89-101, but also towards peptides derived from sequences outside of MBP89-101. These peptides were of two kinds: those with sequences completely outside the 89-101 stretch of MBP; and those sharing a short sequence with MBP89-101 depending on alternative splicing of MBP mRNA. Immunization with these peptides also produced chronic EAE and a spreading of the immune response to other MBP peptides. Immunization with stepped peptides around the relevant region (MBP87-110) showed that peptides sharing a 6-amino-acid motif induced EAE after immunization. After MBP89-101 peptide immunization, T cells isolated from lymph nodes did not cross-react in vitro to the other peptides sharing this motif. We suggest that one mechanism for the development of relapses during the disease course is the recruitment of new T cells with specificity for MBP peptides not derived from the peptide used for immunization. This is the first time such a mechanism has been demonstrated in a chronic autoimmune disease model.

Amino Acid Sequence↗
PubMed1995

Patterns of interferon-gamma mRNA expression in toxic shock syndrome toxin-1 expanded V beta 11+ T lymphocytes.

We have recently demonstrated that toxic shock syndrome toxin-1 (TSST-1), a staphylococcal exotoxin with superantigenic properties, is involved in the pathogenesis of septic arthritis. The aim of the current study was to characterize in detail the in vitro properties of TSST-1 with regard to T cell activation patterns. We demonstrate that TSST-1 preferentially expands murine V beta 11+ T lymphocytes and this expansion occurs equally well within CD4 and CD8 compartments. To analyze the functional properties of V beta 11+ T cells expanded in response to TSST-1, we have utilized a combined in situ hybridization and immunocytochemistry method. With this technique we show that TSST-1-stimulated V beta 11+ T cells are an important source of IFN gamma mRNA synthesis, suggesting that this cytokine may participate in superantigen-mediated septic arthritis.

Animals↗
PubMed1995

PDGF and its receptors following facial nerve axotomy in rats: expression in neurons and surrounding glia.

We investigated the expression of platelet-derived growth factor (PDGF) and its receptors in rat facial nuclei following axotomy by in situ hybridization and immunohistochemistry. Facial nuclei were examined on days 3, 6, 12, 19 and 26 postoperatively (p.o.). Strong immunoreactivity for PDGF was found in facial neurons and surrounding astrocytes on the ipsilateral side of the brainstem already after 3 days p.o. and persisted at a high level until day 26 p.o. in rats with a facial nerve cut injury. After crushing of the facial nerve, a similar increase was seen in PDGF immunoreactivity which, however, decreased after day 19 p.o., when reinnervation had occurred. Reactive gliosis appeared on the operated side and was confirmed by an increase in intensity of GFAP staining. The kinetics of PDGF A-chain mRNA expression corresponded to the PDGF immunoreactivity, whereas the B-chain mRNA was present only in the neurons. The PDGF alpha-receptor immunoreactivity as well as the mRNA were detected in scattered glial cells. The density of the PDGF alpha-receptor mRNA expressing glial cells was higher on the injured side, but the intensity of the expression per cell did not change after axotomy. An increase in PDGF beta-receptor immunoreactivity was seen in the ipsilateral facial nuclei after 3-6 days p.o., however, the increase in the mRNA could not be detected. The staining persisted until day 26 p.o., when transected facial neurons showed heavier staining than those that had been crushed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

B cell responses to acetylcholine receptor in rats orally tolerized against experimental autoimmune myasthenia gravis.

Oral administration of acetylcholine receptor (AChR) to Lewis rats prior to myasthenogenic immunization with AChR and complete Freund's adjuvant (CFA) results in the prevention of experimental autoimmune myasthenia gravis (EAMG), and decreased serum levels of anti-AChR antibodies. Using an ELISPOT assay, we have now determined numbers of cells in the popliteal, inguinal and mesenteric lymph nodes, spleen and thymus secreting anti-AChR IgG antibodies. Except for mesenteric lymph nodes, a marked diminution of such cells was detected in these lymphoid organs in rats orally tolerized with AChR compared to buffer-fed or vehicle-fed control rats with EAMG. Of note is that, after AChR feeding, the B cell response to AChR in thymus was diminished to the same low level as in CFA-injected, buffer-fed control rats. The relative affinity of serum anti-AChR IgG antibodies measured by KSCN-ELISA was lower in the orally tolerized rats compared to buffer-fed or vehicle-fed rats. The observations showed that oral administration of AChR, besides preventing clinical EAMG, also counteracts the development of AChR-specific B cells, especially those with high affinity antibody production, in most lymphoid organs.

Administration, Oral↗
PubMed1995

Suppression of experimental autoimmune myasthenia gravis by nasal administration of acetylcholine receptor.

Experimental autoimmune myasthenia gravis (EAMG) is a well established animal model, which can be induced in various animal species and strains with acetylcholine receptor (AChR) and represents an experimental counterpart of human myasthenia gravis (MG). Current immunotherapies of both EAMG and MG are non-specific and limited by their toxicity. Tolerance to EAMG has been achieved by oral administration of milligram quantities of Torpedo AChR. In the present report we demonstrate that nasal administration of microgram doses of Torpedo AChR to female Lewis rats prior to immunization with Torpedo AChR and complete Freund's adjuvant resulted in the prevention of subsequently induced EAMG, the suppression of serum anti-AChR antibody levels, the decrease of delayed-type hypersensitivity responses to AChR, as well as the suppression of AChR-specific immunoglobulin G-secreting cells, AChR-reactive interferon-gamma-secreting cells and T cell proliferation in peripheral lymphoid organs, particularly in popliteal and inguinal lymph nodes regional to immunization. We conclude that clinical signs of EAMG can be efficiently prevented by nasal administration of AChR in parallel with the downregulation of both B and T cell responses specific to AChR.

Administration, Intranasal↗
PubMed1995

Cytokine production in the central nervous system of Lewis rats with experimental autoimmune encephalomyelitis: dynamics of mRNA expression for interleukin-10, interleukin-12, cytolysin, tumor necrosis factor alpha and tumor necrosis factor beta.

The kinetics of mRNA expression in the central nervous system (CNS) for a series of putatively disease-promoting and disease-limiting cytokines during the course of experimental autoimmune encephalomyelitis (EAE) in Lewis rats were studied. Cytokine mRNA-expressing cells were detected in cryosections of spinal cords using in situ hybridization technique with synthetic oligonucleotide probes. Three stages of cytokine mRNA expression could be distinguished: (i) interleukin (IL)-12, tumor necrosis factor (TNF)-beta (= lymphotoxin-alpha) and cytolysin appeared early and before onset of clinical signs of EAE; (ii) TNF-alpha peaked at height of clinical signs of EAE; (iii) IL-10 appeared increasingly at and after clinical recovery. The early expression of IL-12 prior to the expression of interferon-gamma (IFN-gamma) mRNA shown previously is consistent with a role of IL-12 in promoting proliferation and activation of T helper 1 (Th1) type cells producing IFN-gamma. The TNF-beta mRNA expression prior to onset of clinical signs favours a role for this cytokine in disease initiation. A pathogenic effector role of TNF-alpha was suggested from these observations that TNF-alpha mRNA expression roughly paralleled the clinical signs of EAE. This may be the case also for cytolysin. IL-10-expressing cells gradually increased to high levels in the recovery phase of EAE, consistent with a function in down-regulating the CNS inflammation. From these data we conclude that there is an ordered appearance of putative disease-promoting and -limiting cytokines in the CNS during acute monophasic EAE.

Animals↗
PubMed1995

Glucocorticoids, hippocampal corticosteroid receptor gene expression and antidepressant treatment: relationship with spatial learning in young and aged rats.

The emergence of cognitive deficits in a subgroup of aged rats is associated with increased hypothalamic-pituitary-adrenal axis activity, decreased hippocampal mineralocorticoid and/or glucocorticoid receptor gene expression and neuronal loss. Short-term treatment with antidepressant drugs in young rats increases hippocampal corticosteroid receptor gene expression. In this study, the effects of chronic antidepressant administration on hippocampal mineralocorticoid and glucocorticoid receptor gene expression and spatial memory in young and aged rats were investigated. Young (eight months) and old (22 +/- 1 months) Lister-hooded rats were ranked according to watermaze performance. Matched pairs of rats were treated with amitriptyline (10 mg/kg) or saline daily for nine weeks, then reassessed in the watermaze. Amitriptyline significantly improved spatial memory in the young rats (33% increase in transfer test time) and increased hippocampal mineralocorticoid, but not glucocorticoid receptor messenger RNA expression. By contrast, in aged rats, amitriptyline had no effect on spatial memory or hippocampal corticosteroid receptor gene expression, either in cognitively unimpaired or cognitively-impaired animals. In aged rats, basal plasma corticosterone levels, which were significantly higher than in young animals, correlated negatively with spatial memory, while hippocampal glucocorticoid receptor mRNA expression correlated negatively with plasma corticosterone levels and positively with spatial memory. Amitriptyline had no significant effect on basal morning plasma corticosterone levels in either young or aged rats, but significantly decreased evening corticosterone levels in aged rats. Our data support the notion that corticosterone exerts a concentration-dependent biphasic influence, via selective activation of hippocampal mineralocorticoid and glucocorticoid receptor, on spatial memory. Amitriptyline improves spatial memory in young rats and increases hippocampal mineralocorticoid receptor gene expression. The lack of amitriptyline effect on spatial memory in aged rats may reflect decreased plasticity of both the synaptic processes underlying spatial memory and the regulation of hippocampal mineralocorticoid/glucocorticoid receptor expression, with mineralocorticoid receptors fully occupied due to elevated basal plasma corticosterone levels (in part a consequence of inadequate glucocorticoid receptor function).

Aging↗
PubMed1995

A subtle disturbance in the feedback regulation of the hypothalamic-pituitary-adrenal axis in the early phase of Alzheimer's disease.

In an attempt to find if a disturbance in the function of the feedback regulation of the hypothalamic-pituitary-adrenal axis is an early feature in Alzheimer's disease (AD), 35 outpatients (mean age 76.8 years) with a mild to moderate AD were compared to 20 controls (mean age 73.8 years) in their response to different doses of dexamethasone. After 0.5 mg dexamethasone, serum cortisol levels were significantly less suppressed in patients with early AD (p = .03) and these patients were significantly more often dexamethasone nonsuppressors (serum cortisol > or = 138 nmol/l) than controls (14/35 vs. 2/20; p = .03). Nonsuppression to 1 mg dexamethasone did not differ between groups (2/35 vs. 0/20). Plasma adrenocorticotropin levels were significantly lower in patients with Alzheimer's disease (n = 16) after 0.5 mg as well as after 1.0 mg dexamethasone (p = .01 and p < .001, respectively). The relationship between cortisol resistance to dexamethasone suppression and pathophysiology of AD is discussed.

Adrenocorticotropic Hormone↗
PubMed1995

Abnormalities in adrenal androgens, but not of glucocorticoids, in early Alzheimer's disease.

In an attempt to evaluate possible adrenal abnormalities in Alzheimer's disease (AD), prestimulus levels and ACTH-stimulated serum levels of steroid hormones, corticosteroid-binding globulin (CBG), and insulin-like growth factor I (IGF-I) were measured in 18 patients with early AD (8 men, 10 women; 74.6 +/- 6.5 years, mean +/- SD) and 19 healthy controls (10 men, 9 women; 74.2 +/- 7.6 years, mean +/- SD). Steroid hormone levels were measured before and after an intravenous bolus injection of 250 micrograms ACTH. AD per se had an independent influence on hormone levels when evaluated in MANOVA models. AD patients had significantly higher prestimulus levels of dehydroepiandrosterone and androstenedione (p = .04 and p = .003, respectively) with accentuated differences after ACTH (p = .02 and p < .001 for peak responses, respectively). Serum levels of cortisol, CBG, free cortisol, 17 alpha-hydroxyprogesterone (17 alpha-OHP), and IGF-I did not differ between groups. These abnormalities may have implications for neuronal degeneration as well as for behavioural symptoms in AD.

Adrenal Glands↗
PubMed1995

Axotomy of rat facial nerve induces TGF-beta and latent TGF-beta binding protein.

Transforming growth factor-beta (TGF-beta) has been found to be abundantly and specifically expressed in the nervous system. However, the function of TGF-beta during nerve regeneration is still unknown. We have examined the expression of TGF-beta isoforms and the latent TGF-beta binding protein (LTBP) by immunohistochemistry in the rat facial nuclei after unilateral axotomy. An increased immunoreactivity for all the TGF-beta isoforms and the LTBP was observed in the facial nuclei of the injured side during the regeneration period examined until Day 24. These differences were tested statistically by nominal logistic regression analysis. When the intensity of the immunoreactivity in the injured side was compared to that of the contralateral side, significantly increasing differences were found for TGF-beta 2 (p < 0.003) and LTBP (p < 0.002). Strong immunostaining was detected in the neuronal perikarya and their axons. No clear immunoreactivity was seen in either microglia or astrocytes. The enhanced immunoreactivity was seen in the operated side already at Day 3, remaining at high level with some fluctuations until Day 12 or 24 after axotomy. These findings suggest that TGF-beta might play a functional role in the regeneration of motor neurons.

Amino Acid Sequence↗
PubMed1995

Increased levels of antibodies to IFN-gamma in human and experimental African trypanosomiasis.

In African trypanosomiasis the occurrence of antibodies to interferon-gamma (IFN-gamma) was studied in both humans and experimental rats. Sera from patients infected with Trypanosoma brucei gambiense showed increased levels of antibodies to IFN-gamma as compared with controls from the same regions in Africa. In Sprague-Dawley rats infected with Trypanosoma brucei brucei an early appearance of IFN-gamma-producing spleen cells was observed, followed by an increase in levels of antibodies against IFN-gamma in the sera. Previously, IFN-gamma has been found to play a crucial role in trypanosome infections in rats by promoting proliferation of Trypanosoma brucei brucei. The appearance of antibodies to IFN-gamma in humans, as in rats, indicates that this cytokine is produced also in the human infection. Its parasitic growth-stimulating and pathophysiological effects on the organism may be reduced by the antibodies.

Animals↗
PubMed1995

Increased mRNA expression of IL-10 in mononuclear cells in multiple sclerosis and optic neuritis.

The inflammatory nature of multiple sclerosis (MS) implicates the participation of immunoregulatory cytokines, including the Th2 related IL-10. We describe the use of in situ hybridization with cDNA oligonucleotide probes to detect and enumerate mononuclear cells (MNC) expressing mRNA for IL-10, which is known to down-regulate Th1 cell related cytokines such as interferon-gamma. Expression of IL-10 was studied in blood MNC of MS and blood and cerebrospinal fluid (CSF) MNC of optic neuritis (ON) patients without culture and after culture in the presence of myelin basic protein (MBP), the control antigen acetylcholine receptor (AChR), and without antigen. Numbers of IL-10 mRNA expressing MNC were elevated in the MS patients' blood both when enumerated without culture and after culture with MBP. Control patients with myasthenia gravis had elevated numbers of AChR-reactive IL-10 mRNA expressing cells, while numbers of MBP-reactive IL-10 positive cells did not differ from numbers registered in cells without antigen. Patients with ON, in many instances representing early MS, had IL-10 positive blood MNC that were elevated to the same extent as in clinically definite MS, and further increased in the CSF. ON patients examined within 1 month after onset had lower numbers of MBP induced IL-10 mRNA expressing blood MNC compared with patients examined later suggesting that IL-10 is related to the degree of inflammation and outcome in ON.

Adolescent↗
PubMed1995

Suppression of experimental autoimmune myasthenia gravis after CD8 depletion is associated with decreased IFN-gamma and IL-4.

CD8+ T cells can perform both Th1- and Th2-like functions by producing cytokines such as interferon-gamma (IFN-gamma) and interleukin-4 (IL-4), as well as the immune response down-regulating transforming growth factor-beta (TGF-beta), which are all involved in the development of experimental autoimmune myasthenia gravis (EAMG), a model for human MG. We have reported that depletion of CD8+ T cells results in the suppression of EAMG accompanied by the down-regulation of AChR-specific B cell responses and AChR-reactive IFN-gamma secreting Th1-like cells. To identify the involvement of IFN-gamma, IL-4 and TGF-beta in the development of EAMG after CD8+ T cell depletion, the expression of mRNA for these cytokines was studied in mononuclear cells from popliteal, inguinal and mesenteric lymph nodes, spleen and thymus by adopting in situ hybridization with complementary DNA oligonucleotide probes. Depletion of CD8+ T cells resulted in decreased levels of IFN-gamma and IL-4 mRNA expressing cells in different lymphoid organs except thymus, but no change in the numbers of TGF-beta mRNA expressing cells. The results imply that the suppression of EAMG after depletion of CD8+ T cells is caused by decreasing the effector factors but not by increasing the suppressor factor(s).

Animals↗