Inhibition of experimental autoimmune myocarditis: peripheral deletion of TcR Vβ 8.1, 8.2+ CD4+ T cells in TLR-4 deficient mice
| Autor: | Pedro J. del Nido, Francis X. McGowan, Hanspeter Waldner, Patricia A. Gonnella |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cell Survival Receptors Antigen T-Cell alpha-beta T cell Immunology Biology medicine.disease_cause Severity of Illness Index Autoimmune Diseases Autoimmunity Mice Antigen Myosin medicine Animals Immunology and Allergy Receptor Cells Cultured Mice Knockout Mice Inbred BALB C Toll-like receptor T-cell receptor Wild type Flow Cytometry Molecular biology Peptide Fragments Toll-Like Receptor 4 Disease Models Animal Myocarditis medicine.anatomical_structure Female Gene Deletion Spleen |
| Zdroj: | Journal of Autoimmunity. 31:180-187 |
| ISSN: | 0896-8411 |
| DOI: | 10.1016/j.jaut.2008.06.002 |
| Popis: | Toll-like receptors (TLR) are pattern recognition receptors that are an essential feature of host defense against pathogens. Expression of TLR-4 on dendritic cells was reported to be required for initiation of experimental autoimmune myocarditis (EAM) but the mechanism by which TLR-4 signaling affects autoimmunity is incompletely understood. To determine the role of TLR-4 in EAM, wild type and TLR-4-/- mice were immunized with myosin peptide (614-629) in CFA. TLR-4-/- mice demonstrated decreased myosin specific proliferation and decreased production of INF-gamma and IL-2. Immunization with myosin induced greater severity of myocarditis in wild type compared to TLR-4-/- mice as evidenced by lesions in the myocardium. TcR Vbeta 8.1, 8.2+ CD4+ T cells, detected in lesions were isolated from splenocytes by flow cytometry and found to undergo increased apoptosis in TLR-4-/- mice. In situ immunohistochemistry showed increased colocalization of cleaved caspase 3 and TcR Vbeta 8.1, 8.2+ CD4+ T cells in TLR-4-/- mice compared to wild type. Increased apoptosis was associated with impaired activation of NF-kB p65 and decreased cell viability in the presence of TNF-alpha. These results demonstrate that infiltrating TcR Vbeta 8.1, 8.2+ CD4+ T cells are deleted by the mechanism of apoptosis in TLR-4-/- mice with EAM. |
| Databáze: | OpenAIRE |
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