CD8+ T Cells Contribute to the Development of Coronary Arteritis in the Lactobacillus casei Cell Wall Extract-Induced Murine Model of Kawasaki Disease
| Autor: | Noval Rivas, Magali, Lee, Youngho, Wakita, Daiko, Chiba, Norika, Dagvadorj, Jargalsaikhan, Shimada, Kenichi, Chen, Shuang, Fishbein, Michael C, Lehman, Thomas JA, Crother, Timothy R, Arditi, Moshe |
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| Rok vydání: | 2017 |
| Předmět: |
Cell Extracts
Male Arteritis Animal Clinical Sciences Immunology Coronary Artery Disease CD8-Positive T-Lymphocytes Mucocutaneous Lymph Node Syndrome Inbred C57BL Cardiovascular Autoimmune Disease Arthritis & Rheumatology Mice Lacticaseibacillus casei Heart Disease Cell Wall Disease Models Public Health and Health Services Animals HIV/AIDS 2.1 Biological and endogenous factors Aetiology Lactobacillus casei Heart Disease - Coronary Heart Disease |
| Zdroj: | Arthritis & rheumatology (Hoboken, N.J.), vol 69, iss 2 |
| Popis: | ObjectiveKawasaki disease (KD) is the leading cause of acquired heart disease among children in developed countries. Coronary lesions in KD in humans are characterized by an increased presence of infiltrating CD3+ T cells; however, the specific contributions of the different T cell subpopulations in coronary arteritis development remain unknown. Therefore, we sought to investigate the function of CD4+ and CD8+ T cells, Treg cells, and natural killer (NK) T cells in the pathogenesis of KD.MethodsWe addressed the function of T cell subsets in KD development by using a well-established murine model of Lactobacillus casei cell wall extract (LCWE)-induced KD vasculitis. We determined which T cell subsets were required for development of KD vasculitis by using several knockout murine strains and depleting monoclonal antibodies.ResultsLCWE-injected mice developed coronary lesions characterized by the presence of inflammatory cell infiltrates. Frequently, this chronic inflammation resulted in complete occlusion of the coronary arteries due to luminal myofibroblast proliferation (LMP) as well as the development of coronary arteritis and aortitis. We found that CD8+ T cells, but not CD4+ T cells, NK T cells, or Treg cells, were required for development of KD vasculitis.ConclusionThe LCWE-induced murine model of KD vasculitis mimics many histologic features of the disease in humans, such as the presence of CD8+ T cells and LMP in coronary artery lesions as well as epicardial coronary arteritis. Moreover, CD8+ T cells functionally contribute to the development of KD vasculitis in this murine model. Therapeutic strategies targeting infiltrating CD8+ T cells might be useful in the management of KD in humans. |
| Databáze: | OpenAIRE |
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