Jan Maehlen

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.

Axotomy induces MHC class I antigen expression on rat nerve cells

Immunomorphological staining demonstrates that class I major histocompatibility complex (MHC)-coded antigen expression can be selectively induced on otherwise class I-negative rat nerve cells by peripheral axotomy. Induction of class I as well as class II antigen expression was simultaneously seen on non-neural cells in the immediate vicinity of the injured nerve cells. As nerve regeneration after axotomy includes growth of new nerve cell processes and formation of new nerve cell contacts, the present findings raise the question of a role for MHC-coded molecules in cell-cell interactions during nerve cell growth.

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.

Induction of class I and class II transplantation antigens in rat brain during fatal and non-fatal measles virus infection

Abstract Measles virus induced a marked increase in the expression of MHC-coded class I and class II antigens as detected by immunostaining during both fatal and non-fatal brain infections in rats. The distribution of these molecules in the brain was much more widespread than the occurence of viral antigen suggesting a soluble factor for their induction. In 14-day-old rats with a non-fatal infection there was a marked infiltration of T lymphocytes of ‘cytotoxic/suppressor’ phenotype in the brain parenchyma, whereas T ‘helper’ cell phenotypes mainly were located perivascularly. In brains from newborn rats with a fatal infection no or only few lymphocytes were detected.

Early major histocompatibility complex (MHC) class I antigen induction in hypothalamic supraoptic and paraventricular nuclei in trypanosome-infected rats

Abstract Sprague-Dawley rats were injected intraperitoneally with a suspension of Trypanosoma brucei. An early induction of major histocompatibility complex (MHC) class I antigens as well as an infiltration of macrophage-like and cytotoxic T-cells was detected with immunohistochemical techniques in circumventricular organs, such as the median eminence, neurohypophosis, subformical 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, but project to the neurohypophysis and to the medain eminence, thereby exposing their axon terminals to factors circulating in the blod 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. Sleeping sickness; Trypanosomes; Paraventricular nucleus; Major histocompatibility complex classI

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.

Persistent changes in behaviour and brain serotonin during ageing in rats subjected to infant nasal virus infection

Suckling rats were infected intranasally with the temperature-sensitive mutant G41 strain of vesicular stomatitis virus. The rats survived but demonstrated lifelong learning deficits in the Morris maze and impaired exploratory behaviour in the open field test. When examined at 18 months of age they had a severe loss of neurons in the medial and dorsal raphe nuclei in the brain stem and reduced levels of serotonin and its metabolite 5-hydroxyindole acetic acid in the cerebral neocortex and hippocampus. The levels of noradrenaline, dopamine, homovanillic acid, 3,4-dihydroxyphenylacetic acid, choline acetyltransferase and glutamate decarboxylase were largely unaffected. The permanent disturbance in brain serotonin metabolism did not cause any histological changes in the cerebral cortex. Thus there were no neurofibrillary tangles or amyloid plaques as has been reported as a late effect of chemically induced lesion to the cholinergic system in the rat brain. It is concluded that the brain serotonergic system is especially vulnerable to an episode of virus attack along olfactory pathways and that the neurochemical and behavioural alterations caused by such an episode persist during a major part of the animals life span.

Paramyxovirus infections alter certain functional properties in cultured sensory neurons

Functional properties of cultured mouse dorsal root ganglion cells infected with paramyxoviruses have been studied using intracellular recording techniques. Mumps virus, which causes a persistent non-lytic infection, and Sendai virus, which causes an infection that leads to cell lysis after about a week were used. In the early phase of the infection (24-48 h) both viruses caused a reduction in the influx of calcium ions during the action potential, but did not alter resting membrane potential, action potential amplitude or input resistance. At later times functional properties became normal in mumps infected neurons. In contrast, Sendai virus infected neurons showed a reduction of action potential amplitude and input resistance at 48-72 h after infection, and finally there was also a reduction of membrane potential before the cells disintegrated. These results show that different paramyxovirus infections may cause different types of alterations in the functional properties of neurons. The reduced calcium influx resulting from mumps infection suggests that a non-lytic viral infection may have selective effects on important regulators of neuronal functions. Moreover, a lethal viral infection (Sendai) may influence specific membrane properties, such as calcium channel activation, several days prior to general structural and functional degeneration.

Distribution of leukosialin (W3/13)-like immunoreactivity in the rat central nervous system

SummaryThe 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.