ovalbumin and Neuritis

Schwann cells are the myelinating glia cells of the peripheral nervous system (PNS). In inflammatory neuropathies like the Guillain-Barré syndrome (GBS) Schwann cells become target of an autoimmune response, but may also modulate local inflammation. Here, we tested the functional relevance of Schwann cell derived MHC expression in an in vitro coculture system. Mouse Schwann cells activated proliferation of ovalbumin specific CD8+ T cells when ovalbumin protein or MHC class I restricted ovalbumin peptide (Ova(257-264) SIINFEKL) was added and after transfection with an ovalbumin coding vector. Schwann cells activated proliferation of ovalbumin specific CD4+ T cells in the presence of MHC class II restricted ovalbumin peptide (Ova(323-339) ISQAVHAAHAEINEAGR). CD4+ T-cell proliferation was not activated by ovalbumin protein or transfection with an ovalbumin coding vector. This indicates that Schwann cells express functionally active MHC class I and II molecules. In this study, however, Schwann cells lacked the ability to process exogenous antigen or cross-present endogenous antigen into the MHC class II presentation pathway. Thus, antigen presentation may be a pathological function of Schwann cells exacerbating nerve damage in inflammatory neuropathies.

Topics: Animals; Antigen Presentation; Biomarkers; CD8-Positive T-Lymphocytes; Cell Proliferation; Cells, Cultured; Coculture Techniques; Genetic Vectors; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Lymphocyte Activation; Major Histocompatibility Complex; Mice; Mice, Transgenic; Neuritis; Open Reading Frames; Ovalbumin; Peptide Fragments; Peptides; Peripheral Nerves; Peripheral Nervous System Diseases; Schwann Cells; T-Lymphocytes; Transfection

Exogenously applied tachykinins produce no measurable electrophysiological responses in the somata of vagal afferent neurons [nodose ganglion neurons (NGNs)] isolated from naive guinea pigs. By contrast, after in vitro antigen challenge of nodose ganglia from guinea pigs immunized with chick ovalbumin, approximately 60% (53 of 89) of NGNs were depolarized an average of 13 +/- 1.2 mV by substance P (SP; 100 nM; n = 53). Receptor antagonists and enzyme inhibitors were utilized to screen a number of mast cell-derived mediators for their role in the uncovering or "unmasking" of functional tachykinin receptors after antigen challenge. Two chemically distinct 5-hydroxytryptamine-3-receptor antagonists significantly reduced the percentage of NGNs displaying depolarizing SP responses. Treatment with Y-25130 (1 or 10 microM) or tropisetron (1 microM) 15 min before and during antigen challenge reduced the percentage of SP-responsive neurons to approximately 20 and approximately 15% respectively. These results suggest that activation of 5-hydroxytryptamine-3 receptors plays an integral role in the unmasking of functional tachykinin receptors after specific antigen challenge of nodose ganglia. The mediator(s) underlying tachykinin-receptor unmasking in the remainder of the NGNs has yet to be characterized. However, it does not appear to be histamine, prostanoids, or peptidoleukotrienes.

Topics: Animals; Antigens; Chickens; Electrophysiology; Guinea Pigs; Histamine; Immunization; Leukotrienes; Male; Neuritis; Neurons; Nodose Ganglion; Ovalbumin; Prostaglandins; Receptors, Serotonin; Receptors, Serotonin, 5-HT3; Receptors, Tachykinin; Substance P; Tachykinins

Neural-specific T lymphocytes are held to play a pathological role in inflammatory peripheral nerve disorders such as the Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Here, non-neural-specific T-cell-mediated inflammation was studied in peripheral nerves in Lewis rats by systemic transfer of ovalbumin-specific activated T cells followed by intraneural injection of ovalbumin. Rapid endoneurial perivenular infiltration of alpha beta T cells and ED1+ macrophages occurred with ovalbumin injection following transfer of 2 x 10(6) T cells. This cellular infiltration and accumulation produced marked increases in blood-nerve barrier (BNB) permeability. In contrast, control casein injections produced neither significant cell accumulation nor BNB permeability changes. Transfer of a higher number of T cells (5 x 10(6)) induced severe Wallerian degeneration and nerve conduction failure in ovalbumin injected nerves. Fewer T cells (5 x 10(5)) induced conduction block and mild demyelination which were markedly augmented by systemic cotransfer of anti-myelin immunoglobulin. This study demonstrates that activated T cells of non-neural specificity can accumulate in peripheral nerve, produce dramatic changes in BNB permeability and with intravenous anti-myelin antibody orchestrate primary demyelination or axonal degeneration in a dose-dependent fashion.

Topics: Animals; Blood-Brain Barrier; Dose-Response Relationship, Immunologic; Electrophysiology; Female; Lymphocyte Activation; Myelin Proteins; Neuritis; Ovalbumin; Peripheral Nervous System Diseases; Rabbits; Rats; Rats, Inbred Lew; T-Lymphocytes; Tibial Nerve