Induction of Autoimmune Myocarditis in Interleukin-2–Deficient Mice

Abstract

Our data provide the first genetic evidence that in cardiac myosin-immunized mice, IL-2 has no essential role for the development of autoimmune heart disease and the generation of myosin autoantibodies.

Differential expression of adhesion moleculesshaping the T-cell subset prevalence during the early phase of autoimmune and Trypanosoma cruzi-elicited myocarditis

“…In comparison with the rare inflammatory cells present in the cardiac tissue of CFAinoculated mice, the more pronounced inflammatory foci present in the myocardium of myosin-immunized animals consisted predominantly of macrophages (77.5%), CD4 + T-cells (17.7%) and, to a lesser extent, CD8 + T-cells (4.7%), illustrating a CD4-mediated myocarditis (Fig. 1), as previously described (Grässl et al 1997).…”

“…Immunization with cardiac myosin causes CD4 + T cellmediated acute self-resolving myocarditis in genetically predisposed C3H/He mice and serves as a model for autoimmune heart disease (Pummerer et al 1996, Grässl et al 1997, Wang et al 1999. Herein, we show that the myosin-induced CD4-mediated myocarditis is associated with differential expression of VLA-4 and LFA-1 on circulating CD4 + T lymphocytes, supporting our hypothesis that the differential profile of CAMs expressed by CD4 + T-cells is, at least in part, determinant of their migration into the heart tissue.…”

“…Immunohistochemical characterization of inflammatory infiltrates and CAMs present in the cardiac tissue of myosin-immunized and T. cruzi-infected mice -Groups of 5-15 mice were sacrificed at 7, 14, 21 and 28 days after T. cruzi infection, in order to characterize the kinetic of CD8-mediated myocarditis establishment, and 21 days after myosin immunization, when CD4-mediated myocarditis is established (Grässl et al 1997, Wang et al 1999. Groups of 3 age-matched control mice were sacrificed at the same time-points.…”

Quantitative analysis of small intestinal microcirculation in the mouse

“…A variety of monoclonal antibodies (mAb) directed against mouse antigens has been developed and only recently have gene-targeted mouse strains become available (e.g. disruption of the genes encoding inducible nitric oxide synthase [iNOS], interleukin [IL]-1, IL-2, P-, E-selectin, or ICAM-1) [11,13]. Both functionblocking mAb and the use of gene-targeted animal strains are important tools in biological research, to obtain insight into distinct cellular, humoral, and/or molecular mechanisms encountered under physiological or pathological conditions.…”

The role of caspases in T cell development and the control of immune responses

“…T-cell deletion mediated by TCR cross-linking can be inhibited by injection of neutralizing anti-IL-2 antibodies, and this killing by a self-produced cytokine has been termed propriocidal apoptosis and might be involved in peripheral tolerance to self-antigens. Indeed, mice with either the IL-2 gene or the IL-2 receptor gene disrupted develop autoimmune diseases [87,88]. Cytotoxic T cells (CTLs) are key effectors for the elimination of virus-infected cells, and they deliver a lethal hit to their targets through a calcium-independent pathway involving Fas-FasL or through a calcium-dependent pathway involving granzymes and perforin [89,90].…”