Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study extends the finding that intrathymic (IT) inoculation of uv-B irradiated donor spleen cells (SC) or soluble alloantigens (Ag) induces peripheral tolerance to organ allografts in the rat to the murine cardiac allograft model. In our initial experiment, we showed that IT inoculation of uv-B irradiated SC combined with transient immunosuppression of the recipient with either sublethal TBI or ALS on Day -7 led to donor-specific, long-term cardiac allograft survival (> 300 days) in the completely mismatched A/J-to-C57BL/6 mice combination. To test our hypothesis that peripheral tolerance induced by IT injection of donor Ag is dependent on presentation of the foreign MHC molecule by thymic APC to T cell precursors, we examined the effect of IT injection of donor APC-free-soluble Ag inoculum obtained from 3 MKCl extracts of purified MHC class I resting T cells on cardiac allograft survival in the A/J-to-C3H mice combination. The results showed that IT injection of the optimal dose of 500 micrograms soluble Ag combined with 0.5 ml ALS on Day -7 led to donor-specific permanent graft survival (> 200 days). This finding could not be reproduced by intravenous administration of soluble Ag, thus confirming the privileged position of the thymus in tolerance induction. To further define the role of host APC in allorecognition, we studied the presentation of soluble Ag by responder APC in MLR. The results showed that primed T cells obtained from A/J skin graft-sensitized C3H T cells specifically developed alloreactivity to A/J-soluble Ag in MLR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Donor-specific unresponsiveness to murine cardiac allografts induced by intrathymic-soluble alloantigens is dependent on alternate pathway of antigen presentation. 763 Jan 43

Microglia express many leukocyte surface antigens which are upregulated in such chronic degenerative neurological diseases as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). These surface antigens include leukocyte common antigen, immunoglobulin Fc receptors, MHC class I and class II glycoproteins, beta 2-integrins, and the vitronectin receptor. Ligands for these receptors are also found. They include immunoglobulins, complement proteins of the classical pathway, T lymphocytes of the cytotoxic/suppressor and helper/inducer classes, and vitronectin. T lymphocytes marginate along capillary venules, with some penetrating into the tissue matrix. Immunoglobulins and complement proteins are synthesized locally in brain, although they may also come from the bloodstream if the blood-brain barrier is compromised. The membrane attack complex, which is formed from C5b-9, the terminal components of complement, has been identified in AD and multiple sclerosis brain tissue. In addition, proteins designed to defend against bystander lysis caused by the membrane attack complex, including protectin, C8 binding protein, clusterin, and vitronectin, are associated with damaged neuronal processes in AD. Autodestruction may play a prominent part in these 2 diseases.
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PMID:Microglia in degenerative neurological disease. 842 66

This study extends the finding that intrathymic (IT) injection of 3M KC1 extracts of T cells induces transplant tolerance to the use of well defined polymorphic MHC class I allopeptides derived from the hypervariable domain of RT1.Au (WF MHC class I). While three of the six synthetic RT1.Au peptides were immunogenic, three others were nonimmunogenic when tested in ACI responders. In our initial studies, we examined the effects of IT injection of a mixture of equal concentrations of the three nonimmunogenic RT1.Au peptides on WF cardiac allograft survival in ACI recipients. The results showed that a single IT injection of 100 and 300 microg class I MHC allopeptides on day -7 relative to cardiac transplant did not significantly prolong graft survival in naive ACI recipients (MST of 9.8, and 12.3 days vs. 10.5 days in controls). In contrast, 600 microg allopeptides injected IT resulted in modest prolongation of graft to an MST of 19.5 days. However, IT injection of 600 microg allopeptides combined with 0.5 ml ALS on day -7 led to permanent acceptance (>200 days) of cardiac allografts in 7/9 ACI recipients compared with survival of 24.2 days in ALS alone treated controls. In contrast, similar treatment led to acute rejection of third party (Lewis) cardiac allografts. Intravenous injection of 600 microg allopeptides combined with ALS did not result in prolonged graft survival (26.8 days). The long-term unresponsive ACI recipients (>100 days) challenged with second-set cardiac grafts accepted permanently donor-type (WF) grafts while rejecting the third party (Lewis) grafts, a finding that confirms acquired systemic tolerance. These findings confirm the role of IT injection of synthetic polymorphic allopeptides in the induction of acquired thymic tolerance and provide the rationale for testing this strategy in large animals and eventually in man.
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PMID:Acquired systemic tolerance to rat cardiac allografts induced by intrathymic inoculation of synthetic polymorphic MHC class I allopeptides. 929 86

The low expression of MHC antigens is believed to be one factor of importance contributing to the immune-privileged status of CNS neurons. We here describe that motoneurons, in contrast to other nerve cells in the lumbar spinal cord of the adult rat, express both MHC class I and beta2-microglobulin mRNA. The motoneurons also display in situ hybridization signal for IFN-gamma receptor mRNA. After a peripheral axotomy, the motoneurons show a clear upregulation of beta2-microglobulin mRNA. IFN-gamma treatment of cultured rat embryonic spinal motoneurons causes a similar upregulation of especially beta2-microglobulin. Based on these facts, we propose that spinal motoneurons can be influenced by IFN-gamma and recognized by cytotoxic CD8+ T-cells. These findings could be of relevance in the search for pathogenetic mechanisms in motoneuron-specific diseases, such as ALS.
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PMID:Expression of MHC class I and beta2-microglobulin in rat spinal motoneurons: regulatory influences by IFN-gamma and axotomy. 952 98

We demonstrate here that motoneurons and nigral dopaminergic neurons in the brainstem of the adult rat, with the exception of motoneurons innervating ocular muscles, display high levels of both MHC class I heavy chain and beta2-microglobulin mRNAs. These neurons also display interferon-gamma receptor mRNA. We find it striking that these particular neurons are those which are vulnerable to neurodegeneration in diseases such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS).
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PMID:Expression of MHC class I heavy chain and beta2-microglobulin in rat brainstem motoneurons and nigral dopaminergic neurons. 1058 Aug 16

Posttransplant infusion of donor bone marrow cells (BMC) induces tolerance to allografts in adult mice, dogs, nonhuman primates, and probably humans. Here we used a mouse skin allograft model and an allogeneic radiation chimera model to examine the role of MHC Ags in tolerance induction. Infusion of MHC class II Ag-deficient (CIID) BMC failed to prolong C57BL/6 (B6) skin grafts in ALS- and rapamycin-treated B10.A mice, whereas wild-type B6 or MHC class I Ag-deficient BMC induced prolongation. Removal of class II Ag-bearing cells from donor BMC markedly reduced the tolerogenic effect compared with untreated BMC, although graft survival was significantly longer in mice given depleted BMC than that in control mice given no BMC. Infusion of CIID BMC into irradiated syngeneic B6 or allogeneic B10.A mice produced normal lymphoid cell reconstitution including CD4+ T cells except for the absence of class II Ag-positive cells. However, irradiated B10.A mice reconstituted with CIID BMC rejected all B6 and a majority of CIID skin grafts despite continued maintenance of high degree chimerism. B10.A mice reconstituted with B6 BMC maintained chimerism and accepted both B6 and CIID skin grafts. Thus, expression of MHC class II Ag on BMC is essential for allograft tolerance induction and peripheral chimerism with cells deficient in class II Ag does not guarantee allograft acceptance.
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PMID:Donor MHC class II antigen is essential for induction of transplantation tolerance by bone marrow cells. 1077 44

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motoneuron death. Several cellular pathways have been described to be involved in ALS pathogenesis; however, the involvement of presynaptic stripping and the related MHC class I molecules in mutant SOD1 motoneurons remains to be clarified. To this purpose, we here investigated, for the first time, the motoneurons behavior, di per seand after facial axonal injury, in terms of synaptic stripping and MHC class I expression in wild-type (Wt) mice and in a murine model of ALS, the SOD1(G93A) mice, at the presymptomatic and symptomatic stage of the disease. Concerning Wt animals, we found a reduction in synaptophysin immunoreactivity and an increase of MHC class I molecules in facial motoneurons after axotomy. In uninjured motoneurons of SOD1(G93A) mice, an altered presynaptic framework was evident, and this phenomenon increased during the disease course. The alteration in the presynaptic input is related to excitatory fibers. Moreover, after injury, a further decrease of excitatory input was not associated to an upregulation of MHC class I molecules in motoneuron soma. This study demonstrates, for the first time, that the presence of mutated SOD1 protein affects the MHC class I molecules expression, altering the presynaptic input in motoneurons. Nevertheless, a positive MHC class I immunolabeling was evident in glial cells around facial injured motoneurons, underlying an involvement of these cells in synaptic stripping. This study contributes to better understand the involvement of the mutated SOD1 protein in the vulnerability of motoneurons after damage.
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PMID:The role of mutated SOD1 gene in synaptic stripping and MHC class I expression following nerve axotomy in ALS murine model. 2994 55