Lymbury Robyn S, Olive Colleen, Powell Kellie A, Good Michael F, Hirst Robert G, LaBrooy Justin T, Ketheesan Natkunam
Microbiology and Immunology, School of Biomedical Sciences, James Cook University, Townsville, Australia.
J Autoimmun. 2003 May;20(3):211-7. doi: 10.1016/s0896-8411(03)00026-x.
Rheumatic heart disease (RHD) is considered to be an autoimmune disorder mediated by group A streptococcal (GAS) M protein-specific T cells and antibodies that cross-react with cardiac antigens and epitopes of the GAS M protein. In this study, Lewis rats were immunized with a pool of overlapping peptides spanning the conserved region of the GAS M protein in Complete Freund's Adjuvant, followed by immunization with Bordetella pertussis. Controls received adjuvants alone. Spleen-derived lymphocytes from rats immunized with the conserved region peptides proliferated in response to the immunogen and to cardiac myosin. Moreover, histological examination of cardiac tissue from rats immunized with conserved region peptides revealed the presence of inflammatory lesions in both the myocardium and valve tissue indicating a role for GAS M protein-specific autoreactive T cells in the development of cardiac lesions. This study may support the use of the rat model of autoimmune valvulitis to investigate the immunopathogenesis of RHD and possible preventive strategies.
风湿性心脏病(RHD)被认为是一种自身免疫性疾病,由A组链球菌(GAS)M蛋白特异性T细胞和与心脏抗原及GAS M蛋白表位发生交叉反应的抗体介导。在本研究中,用跨越GAS M蛋白保守区的重叠肽池在完全弗氏佐剂中免疫Lewis大鼠,随后用百日咳博德特氏菌进行免疫。对照组仅接受佐剂。用保守区肽免疫的大鼠脾脏来源的淋巴细胞对免疫原和心肌肌球蛋白发生增殖反应。此外,对用保守区肽免疫的大鼠心脏组织进行组织学检查发现,心肌和瓣膜组织均存在炎性病变,表明GAS M蛋白特异性自身反应性T细胞在心脏病变发展中起作用。本研究可能支持使用自身免疫性瓣膜病大鼠模型来研究RHD的免疫发病机制及可能的预防策略。