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Preparation of CD4+ T Cells for Analysis of GD3 and GD2 Ganglioside Membrane Expression by Microscopy
Published on: November 8, 2016
Thymic alterations in GM2 gangliosidoses model mice.
Seiichi Kanzaki1, Akira Yamaguchi, Kayoko Yamaguchi
1Department of Pathology, Yokohama City University School of Medicine, Yokohama, Japan.
Plos One
|September 22, 2010
Summary
Sandhoff disease in Hexb(-/-) mice shows thymus alterations, including T cell changes and increased macrophages. These autoimmune responses are reduced when FcRγ is disrupted, suggesting its role in thymic autoimmunity.
Area of Science:
- Immunology
- Neuroscience
- Genetics
Background:
- Sandhoff disease is a lysosomal storage disorder caused by absent β-hexosaminidase, leading to GM2 ganglioside accumulation.
- Hexb(-/-) mice, a model for Sandhoff disease, develop progressive neurological decline associated with pathogenic anti-glycolipid autoantibodies.
Purpose of the Study:
- To investigate thymic alterations during the development of neurological disease in Hexb(-/-) mice.
- To identify the role of FcRγ chain in thymic autoimmune responses in Sandhoff disease.
Main Methods:
- Analysis of thymic cellular composition (CD4(+)/CD8(+) and CD4(+)/CD8(-) T cells) in Hexb(-/-) mice.
- Assessment of thymic involution markers, including apoptotic cells and IgG deposits.
- Gene expression profiling using cDNA microarray analysis.
- Evaluation of thymic alterations in FcRγ additionally disrupted Hexb(-/-) mice.
Main Results:
- Hexb(-/-) mice exhibited decreased immature T cells and increased CD4(+)/CD8(-) T cells in the thymus.
- Increased thymic cell apoptosis, IgG deposits on T cells, and swollen macrophages were observed.
- Upregulation of immune response genes, including CXCL13, and increased B1 cells in the thymus.
- FcRγ disruption in Hexb(-/-) mice significantly reduced these thymic alterations.
Conclusions:
- The FcRγ chain may predispose the normally non-immunogenic thymus to autoimmune responses.
- CXCL13 may mediate the chemotaxis of B1 cells within the thymus.
- Targeting FcRγ signaling could be a therapeutic strategy for thymic autoimmunity in Sandhoff disease.
