Single- and multiphoton detachment from stored F- ions.
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Journal Article↗
Biomedical subjects
T Olsson
Publications and source records attributed to T Olsson.
Predominance of Borrelia burgdorferi specific B cells in cerebrospinal fluid in neuroborreliosis.
A nitrocellulose immunospot assay that allows the counting of cells secreting IgG, IgA, or IgM antibodies to Borrelia burgdorferi was used to compare B cell response to B burgdorferi at the cellular level in cerebrospinal fluid (CSF) and blood from patients with neuroborreliosis with that in patients with aseptic meningoencephalitis (AM) or non-inflammatory neurological diseases. 13 of the 14 patients with untreated neuroborreliosis had CSF cells secreting IgG antibodies to B burgdorferi (mean 17 cells per 10(4) CSF cells), whereas 8 of 12 patients examined had cells secreting IgA antibodies (mean 6 cells) and 10 of 12 had cells secreting IgM antibodies (mean 6 cells) per 10(4) CSF cells. IgG antibody producing cells predominated except in 2 patients with mainly or only IgM secreting cells. Cells secreting antibodies to B burgdorferi were rarely found in the blood and then at very low numbers, which reflects preferential compartmentalisation of the specific B cell response to the CSF. The cells were not detectable in CSF or blood from the two control groups. Evaluation of humoral immunity at the cellular level is a novel approach to the detection and localisation of immune events in neuroinflammatory disorders.
Adolescent↗
Peripheral nerve injury causes transient expression of MHC class I antigens in rat motor neurons and skeletal muscles.
After a peripheral nerve lesion (rat facial and sciatic) an induction of major histocompatibility complex (MHC) antigens class I was detected immunohistochemically in skeletal muscle fibers and motor neurons. This MHC expression was transient after a nerve crush, when regeneration occurred, but persisted after a nerve cut, when regeneration was prevented. Since the time course of MHC class I expression correlates to that of regeneration a role for this cell surface molecule in regeneration may be considered.
Animals↗
Mononuclear cell types in cerebrospinal fluid and blood of patients with multiple sclerosis. Quantitation by immunoenzyme microassay with panel of monoclonal antibodies.
Phenotypic distribution of mononuclear cells in cerebrospinal fluid (CSF) and peripheral blood from patients with multiple sclerosis (MS) and, for reference, patients with acute aseptic meningoencephalitis (AM), and in blood only from healthy controls, was studied with an immunoenzymatic microassay enabling analysis even in the presence of a normal CSF cell count. In MS, increased CD5+ (pan-T) cell proportion in CSF compared with blood was not reflected by changes of CD4+ or CD8+ cells, while in AM, an increase of CD4+ cells was registered. Therefore, a population of CD5+, CD4-, and CD8- cells may be anticipated to exist in CSF of patients with MS. Numbers of OKB7+, OKM1+, or HLA-DR+ cells did not distinguish between MS and AM. Proliferating cells expressing transferrin receptors (OKT9+ cells) were generally few or absent in CSF and not useful as a marker of disease activity in either MS or AM.
Acute Disease↗
Interferon-gamma-like immunoreactivity in certain neurons of the central and peripheral nervous system.
Interferon-gamma (IFN-gamma) has many important immunoregulatory functions. It has previously been presumed to be produced by activated lymphoid cells alone. The present study concerning the identification of IFN-gamma in neurons was initiated against the background that nerve function influences immunological events during inflammatory diseases. Furthermore, the immune system and the nervous system may have certain signal molecules as well as certain cell surface receptors in common. Neuronal IFN-gamma-like immunoreactivity (IFN-gamma-LI) was studied in frozen sections of rat tissues employing both rabbit polyclonal antiserum as well as seven different mouse monoclonal antibodies (mAbs) reactive with different epitopes of rat IFN-gamma. The polyclonal antiserum and three of the mAbs (DB-1, DB-14, and DB-16) showed IFN-gamma-LI in neurons. DB-1, the most extensively studied mAb, stained distinct networks of nerve terminal-like profiles both in the brain and spinal cord. Also, scattered brain neuronal cell bodies showed IFN-gamma-LI as well as a subpopulation of primary sensory ganglion cells and their intra CNS terminals. In addition, IFN-gamma-LI was also detected in nerve terminal-like profiles in skin, gut, and lymphoid organs. Terminals were especially prominent around blood vessels. We propose that IFN-gamma has a role in cell interactions not only in the immune system but also in the nervous system as well as in interactions between the nervous and immune systems.
Animals↗
Distribution of leukosialin (W3/13)-like immunoreactivity in the rat central nervous system.
The monoclonal antibody W3/13, which is directed against leukosialin (a molecule present on certain types of leukocytes), was found to react immunohistochemically with distinct regions and structures in the rat CNS. The leukosialin (W3/13)-like immunoreactivity occurred on neurite-like fibres and on bouton-like structures on nerve cell bodies and their dendrites. This labelling was most pronounced in certain subcortical areas and brain stem nuclei including different thalamic nuclei, olfactory tubercle, superior olive, cochlear and vestibular nuclei, motor and somatosensory nuclei. In the cerebellum, immunoreactive fibres were prominent in the molecular layer. In the spinal cord there was a dense labelling of fibres in the whole grey matter.
Animals↗
Distribution of plasma cells secreting antibodies against nervous tissue antigens during experimental allergic encephalomyelitis enumerated by a nitrocellulose immunospot assay.
The B cell response to central nervous system (CNS) myelin and myelin basic protein, as well as total numbers of IgG secreting cells, was studied in acute experimental allergic encephalomyelitis using a nitrocellulose immunospot assay. The method was able to detect single plasma cells secreting antibodies. Cells secreting antibodies against myelin antigens were detected in regional lymph node cell suspension by day 5 post-immunization (p.i.). At that time no anti-myelin antibodies were detected free in serum. Later, at day 15 p.i., specific antibody secreting cells were found in bone marrow and spleen indicating a generalization of the immune response. The B cell response became partly sequestered to the target of immune attack since an increased number of IgG secreting cells was detected among mononuclear cells recovered from the CNS. Studies of cellular secretion of antibodies rather than free levels in body fluids may be a more accurate reflection of the in vivo B cell response. These findings may be generally considered in studies of B cell mediated immunity in neuroinflammatory diseases.
Animals↗
Local enhancement of major histocompatibility complex (MHC) class I and II expression and cell infiltration in experimental allergic encephalomyelitis around axotomized motor neurons.
The effect of unilateral peripheral nerve lesions on the inflammatory response of experimental allergic encephalomyelitis (EAE) in rat central nervous system (CNS) was studied. Immunostaining for major histocompatibility complex (MHC) antigens and T-cell subsets demonstrated that MHC class I expression was markedly enhanced in as well as around axotomized motor neurons and that MHC class II expression was induced on several cells, probably microglial cells, in close proximity to the axotomized motor neurons. There was also a pronounced increase in interleukin 2 receptor-positive lymphocytes as well as T-cells and the T-cell subsets on the injured as compared to the non-injured contralateral side. These effects were present particularly in the initial phase of EAE and persisted for several weeks. The results suggest that neurons may communicate immunoregulatory signals to their microenvironment and that retrograde axonal signals from the distant periphery may alter the immune response locally within the CNS.
Animals↗
In vivo monoclonal antibody treatment with Ox19 (anti-rat CD5) causes disease relapse and terminates P2-induced immunospecific tolerance in experimental allergic neuritis.
The role of CD5+ lymphocytes in the recovery phase and on immunospecific protection against experimental allergic neuritis (EAN) was examined in Lewis rats by in vivo treatment with Ox19, a mouse anti-rat CD5 monoclonal antibody. Animals pretreated with the peripheral nerve basic protein P2 and thereby rendered resistant to the disease showed clinical signs of EAN after intraperitoneal (i.p.) Ox19 injection given at the same time as the rechallenge with neuritogenic doses of myelin in Freund's complete adjuvant. Non-pretreated rats recovered from signs of EAN developed a clinical relapse after i.p. Ox19 injections. Taken together, these data suggest an important regulatory role of the CD5 receptor in the immune response.
Animals↗
Immunoglobulin-secreting cells in the cerebrospinal fluid from patients with muscular tension headache.
Intrathecal B cell function in healthy subjects has been poorly elucidated. Although there are measurable quantities of immunoglobulins (Ig) in the cerebrospinal fluid (CSF) of 'normal' individuals, it is not clear whether this reflects transudation from serum or is due to some production within the central nervous system. We have therefore isolated cells from CSF to assess the frequency of Ig-secreting cells, utilizing a nitrocellulose immunospot assay for enumeration of the IgG-, IgA- and IgM-producing cells per 10(4) mononuclear cells (MNC) isolated from CSF and blood. Contrary to previous belief, the CSF obtained from 22 of 23 'normal' subjects (95%) with muscular tension headache but no evidence of organic neurological disease contained 2-50 (mean 20) IgG-secreting cells per 10(4) MNC. The corresponding peripheral blood specimens contained 0-6 (mean 3) IgG-secreting cells per 10(4) MNC. The proportion of IgG-secreting cells among MNC is thus about 7-fold higher in CSF than in blood of healthy individuals. IgA- and IgM-producing cells were also found in normal CSF, but less frequently than cells secreting IgG and at proportions similar to those in peripheral blood. We suggest that there is continuous production of Ig of different isotypes in CSF, even in subjects without any signs of neurological disease.
Adult↗
Early major histocompatibility complex (MHC) class I antigen induction in hypothalamic supraoptic and paraventricular nuclei in trypanosome-infected rats.
Sprague-Dawley rats were injected intraperitoneally with a suspension of Trypanosoma brucei brucei. An early induction of major histocompatibility complex (MHC) class I antigens as well as an infiltration of macrophage-like cells and cytotoxic T-cells was detected with immunohistochemical techniques in circumventricular organs, such as the median eminence, neurohypophysis, subfornical organ, pineal gland and area postrema. These areas, which lack a blood-brain barrier, correspond to those showing early invasion of trypanosomes. In addition, there was a marked induction of MHC class I in neurons in two hypothalamic nuclei, the paraventricular and supraoptic nuclei. Neurons in these two nuclei are located behind the blood-brain barrier, but project to the neurohypophysis and to the median eminence, thereby exposing their axon terminals to factors circulating in the blood or released locally from invading trypanosomes or from macrophages or cytotoxic T-cells. It is suggested that the alteration in the nerve cell bodies in the hypothalamic nuclei is caused by retrograde axonal signals from these target areas.
Animals↗
Persistence of measles virus in rat brain neurons is promoted by depletion of CD8+ T cells.
Fourteen-day-old Lewis rats were injected intracerebrally with the hamster neurotropic (HNT) strain of measles virus. At the same time, CD8+ T cytotoxic cells were eliminated by a single injection of a mouse monoclonal antibody (Ox8) directed against this lymphocyte phenotype. The lymphocyte depletion, which endured for more than 7 weeks, markedly reduced the elimination of measles virus antigen from the brain, but did not affect the induction of major histocompatibility complex (MHC) molecules in the early phase of infection. These results demonstrate a role for MHC class I-restricted CD8+ T cells in controlling persistence of measles virus infection in neurons.
Animals↗
B cells and antibodies in MS.
When the B-cell response was examined by enumeration of immunoglobulin (Ig)-secreting cells, normal cerebrospinal fluid (CSF)--in contrast to previous beliefs--contained IgG-secreting cells, indeed at an 8-fold higher proportion per 10(4) mononuclear cells (MNC) than blood. As expected, the proportion of IgG-producing cells was greatly increased in MS CSF. Evaluation of antibody (Ab) responses at the cellular level, thereby bypassing draw-backs inherent in determinations of circulating Ab levels, such as Ab binding to target, revealed that in one MS patient group, 57% had, in CSF, cells secreting IgG Ab against myelin basic protein (MBP) and, in another MS group, 55% had, in CSF, cells producing IgG Ab against myelin-associated glycoprotein (MAG); both MBP and MAG are possible targets for immune attack in MS. Anti-MBP and anti-MAG IgG antibody-secreting cells could occur in parallel or independently. They were rarely detected in blood, reflecting strong sequestration in CNS CSF. Their possible role in MS pathogenesis is envisaged in light of recently suggested coupling between polyclonal B-cell hyperresponsiveness and antigen-driven specific responses in autoimmune-prone individuals.
Antibody Formation↗
Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities.
HLA class II gene polymorphism was investigated in 100 patients with clinically definite multiple sclerosis (MS) by restriction fragment length polymorphism analysis of Taq I-digested DNA using DRB, DQA, and DQB cDNA probes. Twenty-six patients had primarily chronic progressive MS and 74 had relapsing/remitting MS. The latter group included patients with a secondary progressive evolution of symptoms. Both clinical forms of MS were found to be associated with the DRw15,DQw6 haplotype. In addition, primarily chronic progressive MS was positively associated with the DQB1 restriction fragment pattern seen in DR4,DQw8, DR7,DQw9, and DRw8, DQw4 haplotypes, as well as negatively associated with the Taq I DQB1 allelic pattern corresponding to the serological specificity DQw7. Relapsing/remitting MS was positively associated with the DQB1 allelic pattern observed in the DRw17,DQw2 haplotype. These three DQB1 alleles are in strong negative linkage disequilibria with DRw15. The two susceptibility markers of each clinical form of MS act additively in determining the genetic susceptibility, as the relative risks for individuals carrying both markers roughly equal the sum of respective risks. Different alleles of the DQB1 locus defined by restriction fragment length polymorphisms contribute to susceptibility and resistance to primarily chronic progressive MS as well as to susceptibility to relapsing/remitting MS. The observed immunogenetic heterogeneity between the different clinical forms of MS favors the hypothesis that primarily chronic progressive MS and relapsing/remitting MS are two distinct disease entities.
Alleles↗
Effect of ion channel blockers on immune response and course of experimental allergic neuritis.
The influence of the K+ channel blocker quinidine and the Ca++ channel blocker verapamil on in vivo and in vitro immune responses was tested in experimental allergic neuritis (EAN) of Lewis rats. Daily intraperitoneal injections of 4 mg quinidine produced a significant reduction of neurological deficits in EAN rats, whereas verapamil had no effect. In contrast, both drugs inhibited the in vitro proliferative response of regional lymph node cells to specific antigens of bovine peripheral myelin and purified protein derivative of tuberculin in a similar dose-dependent manner. Quinidine-treated EAN rats revealed considerably less inflammatory infiltration in target tissue than untreated EAN rats, shown immunohistochemically. Single injections of ion channel blockers into EAN rats did not improve nerve cell functions as measured by electrophysiological recordings of sciatic nerve. It is concluded that the dominant effect of quinidine in vivo is attributed to a reduction of the demyelinating autoimmune process. Hence ion channel blocking drugs can exert immunomodulatory effects, which may have implications for their clinical application.
Animals↗
Leukocyte types in cerebrospinal fluid and peripheral blood enumerated immunoenzymatically in aseptic meningitis and the Guillain-Barré syndrome.
To study celltype distribution simultaneously in peripheral blood (PB) and cerebrospinal fluid (CSF) from patients with aseptic meningitis (AM) (n = 14) and Guillain-Barré syndrome (GBS) (n = 9) we used an immunoenzymatic method that enabled the use of several monoclonal antibodies, also in CSF samples with normal cellcounts. In both patient groups a different cell-distribution in CSF compared to PB was found with regard to pan T cells (CD5+/anti-Leu1+), T cell subpopulations (CD4+/anti-Leu3+, CD8+/anti-Leu2+), B cells (OKB2+, OKB7+), monocytes/macrophages (CD11+/OKM1+) and HLA/DR expressing cells, whereas the distribution of HLA/DC+ cells was similar in CSF and PB. Thus, the CSF cell distribution does not reflect the distribution in PB. The proportion of T cells was higher and the proportion of B-cells was lower in CSF than in PB in both patient groups, which is a finding similar to that in patients with multiple sclerosis. The OKT9 marker, labelling proliferating cells expressing the transferrin receptor, was not useful as marker of local proliferation.
Adult↗
In vivo treatment of rats with monoclonal antibodies against gamma interferon: effects on experimental allergic neuritis.
To elucidate the role of gamma interferon in experimental allergic neuritis (EAN) a mouse monoclonal antibody (DB-1) directed against rat gamma interferon was used to treat rats during different phases of the development of experimental allergic neuritis (EAN). The effects of this treatment were followed by clinical evaluation, and in some instances by immunohistochemical analysis of lymphoid organs and affected nerves for presence of MHC class II antigens and various T cell subsets. DB-1 treatment given after onset of clinical symptoms (Day 15 after immuniozation with myelin) shortened disease duration, compared with non-treated EAN controls. Affected nerves of DB-1 treated animals showed reduced expression of MHC class II antigens and lower numbers of T lymphocytes within the affected nerves. In contrast, when DB-1 treatment was given on the day of immunization (Day 0), the disease duration increased, and when given before onset of the disease (Day 9) the clinical course was not significantly affected. The results support an important role for gamma interferon in the pathogenesis of EAN.
Animals↗
Hormones in 'young' and 'old' elderly: pituitary-thyroid and pituitary-adrenal axes.
Changes of the pituitary-thyroid and pituitary-adrenal hormone axes with age and possible differences between the sexes in the elderly were studied in 60-year-old (n = 39) and 80-year-old (n = 34) non-hospitalized subjects. The 80-year-old age group had a significantly lower response of thyrotropin (TSH) to thyrotropin-releasing hormone (TRH; p less than 0.05). Otherwise, there were no significant differences between the two age groups. Sex differences were found for plasma arginine vasopressin and cortisol excretion (higher values in men), and free thyroxine index, TSH and prolactin response to TRH (higher values in women). Cortisol levels after dexamethasone were negatively correlated to body mass index. There were no differences in hormone levels between smokers and non-smokers. In obtaining reference values for hormones in old age it is important to consider possible changes after the age of 60 years and to adjust for gender and body mass.
Aged↗