Rat Schwann cells produce interleukin-1.

There is increasing evidence that Schwann cells of peripheral nerves may be able to function as accessory cells, interacting with the immune system in T cell-mediated immune responses, by expression of the major histocompatibility complex (MHC) class II molecules. In addition to MHC class II-associated presentation of antigen to T lymphocytes, the release of a co-stimulatory factor, interleukin-1 (IL-1), is an essential function of accessory cells for T cell activation. In this study, we investigated if Schwann cells were able to produce IL-1. Purified cultures of neonatal and adult rat Schwann cells were incubated with various stimulatory agents. Supernatants and cell lysates were collected from these cultures and IL-1 activity was assayed. Both neonatal and adult rat Schwann cells produced IL-1 activity in response to bacterial antigens and the IL-1 activity was often higher in the cell lysate than in the supernatant. When stimulated neonatal or adult rat Schwann cells were examined with antibody against IL-1, strong immunolabelling was seen intracellularly, but no IL-1 was detected on the cell surface. Since IL-1 plays an important role in the initiation of immune responses, these observations support the view that Schwann cells may function as antigen-presenting cells, thereby taking part in neuroimmunological responses within peripheral nerves.

Genetic linkage analysis of the antibody responses to myelin basic protein and myelin oligodendrocyte glycoprotein in rats immunized with rat spinal cord homogenate.

The genetic control of the antibody response to myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) was analysed in F1 and F2 crosses of DA and E3 rats, immunized with rat spinal chord homogenate. The DA rats were highly susceptible to encephalomyelitis and made antibody responses to both MBP and MOG, whereas the E3 rats were disease-resistant and responded only to MOG. The anti-MBP response was mainly controlled by the disease-promoting MHC region of the DA strain together with several disease loci outside MHC. In contrast, the anti-MOG response was associated with loci not related to or actually conferring resistance to disease.

Rat Schwann cells can be induced to express major histocompatibility complex class II molecules in vivo.

Previous studies, showing that cultured rat Schwann cells could be induced to express MHC class II molecules, raised the possibility that Schwann cells in living nerves might, under some conditions, express MHC class II molecules and take part in activation of T lymphocytes. In the present work, the ability of myelin- and non-myelin-forming Schwann cells in vivo to express MHC class II molecules was investigated. Lymphokines or bacterial antigens were injected into the living sciatic nerve of adult rats. Examination of the nerves three days after injection of interferon-gamma or six days after injection of either tumour necrosis factor, antigens from mycobacterium leprae or whole mycobacteria leprae, revealed strong MHC class II immunostaining on some myelin-forming Schwann cells in the vicinity of the injection site. Very few non-myelin-forming cells expressed MHC class II molecules. MHC class II positive mononuclear cells were present in the injected nerves and endothelial cells of capillaries expressed high levels of MHC class II antigens. Crushing the sciatic nerve without injection of factors also induced MHC class II molecules on a few Schwann cells. Thus rat Schwann cells can be induced to express MHC class II molecules in vivo as in vitro. This strengthens the possibility that in living nerves Schwann cells are able to function as accessory cells in the initiation or augmentation of T cell-mediated immune responses.

Evidence for common autoimmune disease genes controlling onset, severity, and chronicity based on experimental models for multiple sclerosis and rheumatoid arthritis.

The pathogenicity of multiple sclerosis is still poorly understood, but identification of susceptibility genes using the animal model experimental allergic encephalomyelitis (EAE) could provide leads. Certain genes may be shared between different autoimmune diseases, and identification of such genes is of obvious importance. To locate gene regions involved in the control of EAE and to compare the findings with the susceptibility loci recently identified in a model for rheumatoid arthritis (pristane-induced arthritis), we made crosses between the encephalomyelitis- and arthritis-susceptible rat strain DA and the resistant E3 strain. Genetic analysis of animals produced in a F2 intercross identified 11 loci associated with specific EAE-associated traits. Interestingly, five of these loci were situated at the same position as major loci controlling pristane-induced arthritis and showed similarities in inheritance pattern and subphenotype associations. Our results show that different phases of EAE are controlled by different sets of genes and that common genes are likely to be involved in different autoimmune diseases.

The effect of three dimensional collagen type I preparation on the structural organization of guinea pig enteric ganglia in culture.

In vivo, cellular relationships in the myenteric plexus are characterized by unusual compactness and by the arrangement of neurons and glia into ganglia and interconnecting strands. These features are lost when the myenteric plexus is placed in culture. In the present paper we test whether collagen type I, a major component of the matrix that surrounds the plexus in vivo, might have a role in maintaining normal neuron-glia relationships in this system. We report that a three-dimensional gel of rat tail collagen prevented the disaggregation of the guinea pig myenteric plexus in culture and induced the formation of a compact plexus-like cellular network when applied to disaggregated plexus cultures. These effects were not observed with soluble collagen. Immunohistochemical evidence was also obtained for synthesis of type I collagen by enteric glia. These observations indicate that type I collagen in a three-dimensional organization is capable of inducing and maintaining both the unusual compact organization of neurons and glial cells within myenteric ganglia and also the characteristic organization of these cells into an orderly network of ganglia and interconnecting strands.

Constitutive and visna virus induced expression of class I and II major histocompatibility complex antigens in the central nervous system of sheep and their role in the pathogenesis of visna lesions.

Expression of major histocompatibility complex (MHC) antigens was studied in the brains of 10 healthy sheep 2 months to 5 years old and 13 sheep infected with visna virus by intracerebral inoculation and killed one and 6 months post infection (p.i.). In healthy sheep there was prominent expression of class I, mainly on endothelial cells but also detected on ependyma, choroid plexus and in the leptomeninges. Class II expression was sparse. It was observed on perivascular cells, in choroid plexus, leptomeninges and on microglial cells in the white matter. No definite increase with age in the constitutive expression of class I and II was observed, confirming that we are dealing with a true constitutive expression. In visna-infected sheep a considerable induction of MHC antigens on microglia was observed, which correlated with severity of lesions and was mainly found in or adjacent to inflammatory infiltrates of the white matter. Increase in class II antigen expression was detected in all sheep but class I only in sheep with the most severe lesions 6 months p.i., an indication of a higher threshold for induction of class I than class II antigens on microglia. Few cells expressed viral antigens, indicating that direct immune-mediated destruction of infected cells plays a minor role in evolution of lesions. Since the preferential induction of MHC antigens on microglia in the white matter correlated with the lesion pattern, activated microglia may play a considerable role in the pathogenesis of lesions.

Schwann cells co-cultured with stimulated T cells and antigen express major histocompatibility complex (MHC) class II determinants without interferon-gamma pretreatment: synergistic effects of interferon-gamma and tumor necrosis factor on MHC class II induction.

Schwann cells (SC) do not express major histocompatibility complex (MHC) class II antigens under normal culture conditions. SC can, however, be induced in vitro to express MHC class II molecules by exposure to high concentrations of interferon-gamma (IFN-gamma) and can present antigens to antigen-specific T cell lines. In the present study immunohistochemical labeling showed that most SC (greater than 90%) prepared from rat neonatal sciatic nerves expressed MHC class II molecules when cultured together with mycobacterial antigen and T cells, and as a consequence were able to function as antigen-presenting cells in lymphoproliferation assays, without requiring pretreatment with IFN-gamma. Antigen or T cells alone were ineffective in stimulating MHC class II expression and induction of class II molecules was MHC restricted, requiring the presence of syngeneic T cells. Addition of monoclonal antibody DB1, directed against IFN-gamma to co-cultures of SC and T lymphocytes stimulated with antigen, prevented the induction of MHC class II antigen on SC. When SC were incubated with recombinant (r)IFN-gamma alone, up to 50% of SC showed positive labeling for MHC class II antigen. This level of expression was enhanced to greater than 80% when recombinant tumor necrosis factor (rTNF) was also added. rTNF alone had no effect, and addition of DBI antibody inhibited the synergistic effects of rTNF on MHC class II expression. The effects of rIL 4 were also investigated but neither rIL 4 alone nor rIL 4 in combination with rIFN-gamma induced MHC class II expression by SC. These results show that in the presence of sensitized T lymphocytes and antigen, SC do not require pretreatment with exogenous rIFN-gamma to express MHC class II antigens and function as antigen-presenting cells. T cell-derived TNF and IFN-gamma appear to act as mediators of the T cell-induced expression of MHC class II by SC.