Cross-presentation as a fundamental pathway of activating CD8 ؉ T cells has been well established. So far the application of this concept in vivo is limited, and the mechanisms that specialize CD8 ؉ dendritic cells (DCs) for this task are not fully understood. Here we take advantage of the specific cytosolic export feature of crosspresenting DCs together with the property of cytosolic cytochrome c (cyt c) in initiating Apaf-1-dependent apoptosis selectively in cross-presenting DCs. A single i.v. injection of cyt c in B6 mice produced a 2-to 3-fold reduction in splenic CD8 ؉ DCs but not in Apaf-1-deficient mice. Functional studies both in vivo and in vitro showed that cyt c profoundly abrogated OVA-specific CD8 ؉ T cell proliferation through its apoptosis-inducing effect on crosspresenting DCs. More importantly, in vivo injection of cyt c abolished the induction of cytotoxic T lymphocytes to exogenous antigen and reduced subsequent immunity to tumor challenge. In addition, only a proportion of CD8 ؉ DCs that express abundant IL-12 and Toll-like receptor 3 were efficient cross-presenters. Our data support the hypothesis that cross-presentation in vivo requires cytosolic diversion of endocytosed proteins, conferring cross-presentation specialization to a proportion of CD8 ؉ DCs. We propose that DCs incapable of such transfer, even within the CD8 ؉ DC subset, are unable to cross-present. Our model opens an avenue to specifically target cross-presenting DCs in vivo for manipulating cytotoxic T lymphocyte responses toward infections, tumors, and transplants.antigen presentation ͉ apoptosome ͉ cytotoxic T cells

Non-compaction of the ventricular myocardium is a rare congenital cardiomyopathy that carries an unfavorable prognosis. It is associated with a high incidence of progressive heart failure, thromboembolism and malignant arrhythmias. Echocardiography currently remains the imaging modality most commonly used for diagnosis. We describe an unusual case of isolated non-compaction of the left ventricle in an octogenarian male to highlight the need for echocardiography in all patients with suspected heart failure, in order to determine aetiology, prognosis and assess treatment.

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