A line of nonobese diabetic (NOD) mice expressing the human diabetes-associated HLA-DQ8 transgene in the absence of mouse IA failed to show spontaneous insulitis or diabetes, but rather developed dilated cardiomyopathy, leading to early death from heart failure. Pathology in these animals results from an organ-and cell-specific autoimmune response against normal cardiomyoctes in the atrial and ventricular walls, as well as against very similar myocytes present in the outermost muscle layer surrounding the pulmonary veins. Progression of the autoimmune process could be followed by serial ECG measurements; irradiation of young animals significantly delayed disease progression, and this effect could be reversed by adoptive transfer of splenocytes taken from older animals with complete heart block. Disease progression could also be blocked by cyclosporin A treatment, but was accelerated by injection of complete Fruend's adjuvant. The constellation of findings of spontaneously arising destructive focal lymphocytic infiltrates within the myocardium, rising titers of circulating anticardiac autoantibodies, dilation of the cardiac chambers, and gradual progression to end-stage heart failure bears a striking resemblance to what is seen in humans with idiopathic dilated cardiomyopathy, a serious and often life-threatening medical condition. This transgenic strain provides a highly relevant animal model for human autoimmune myocarditis and postinflammatory dilated cardiomyopathy.I diopathic dilated cardiomyopathy (IDCM) describes a condition whereby previously healthy individuals develop lifethreatening heart failure associated with enlargement of the heart, but with no apparent underlying cause (1, 2). The cardiac pathology seen in the majority of IDCM patients indicates a recent or more long-standing immune-mediated inflammatory process within the muscle tissue of the heart (i.e., myocarditis) (3,4). IDCM patients often demonstrate circulating anticardiac autoantibodies, and the myocarditis is generally thought to arise from an autoimmune response against cardiac tissues (5). Research on IDCM has been hampered by the lack of an appropriate animal model, that is, a model where animals develop disease spontaneously, show severe life-threatening pathology, and display an immunological and histological picture similar to that seen in humans with IDCM.The human MHC class II molecule DQ8 (i.e., haplotype DQA1*0301, DQB1*0302) is known to be associated with type 1 diabetes (T1D). To map DQ8-restricted T cell epitopes for T1D autoantigens we crossed DQ8 transgenic nonobese diabetic (NOD) mice with a NOD MHC class II -chain knockout line (6). Because the resulting animals express the human MHC class II molecule but not the mouse, any CD4 ϩ T cells arising would be restricted to the human MHC molecule. We chose the NOD strain because it is known to have defects in self-tolerance, which we hypothesized would aid our efforts to induce immune responses against self-antigens such as GAD65. Although replacement of the murine T1D-asso...
HIV infection is associated with increased numbers of mast cells, macrophages and neutrophils in the chronic periodontal lesion. This may predispose for tissue destruction through the release of inflammatory mediators and effector molecules. The unusually heavy cell infiltrate throughout the gingival connective tissue may contribute to the diverging pattern of periodontal tissue loss in HIV-positive patients.
The findings suggest that the oral gingiva in HIV+ patients may be affected by inflammation.
The topical distribution of Fc gamma receptor types I, II and III (Fc gammaRI-III) was analyzed by means of immunohistochemistry in human gingival tissue obtained from 12 patients with chronic periodontitis. CD68+ macrophages expressing all three classes of Fc gammaR were found throughout the whole gingival connective tissue (CT), whereas dense infiltrates of polymorphonuclear granulocytes (identified by staining for neutrophil elastase) with strong staining for Fc gammaRIII and Fc gammaRII were found subjacent to the apical part of the pocket epithelium (PE) and in the PE itself. CD19+ B lymphocytes with variable staining intensity for Fc gammaRII were observed in clusters subjacent to the PE and extending into the central part of the CT. Only a few scattered CD3+ T lymphocytes stained for Fc gammaRIII. Some spindle-shaped cells (CD68-, therefore non-macrophages) and apparently non-cellular fibrous tissue elements stained for Fc gammaRI and Fc gammaRII. In the epithelium, Fc gammaRII+ dendritic cells were frequently observed in the entire oral gingival epithelium and in the coronal part of the PE. Occasionally, some keratinocytes which stained for Fc gammaRII and Fc gammaRIII were found. The observations indicate that Fc gammaR of the various classes are amply expressed on numerous cell types in inflamed gingival tissue. The specific distribution pattern detected suggests that Fc gammaRs may play a role in the mediation of chronic inflammation in the periodontal lesion.
It is suggested that FcalphaRI on neutrophils may play an important rôle in elimination of IgA-opsonized bacteria, both in periodontal tissue and the adjacent pockets.
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