Cell apoptosis and granulomatous lung diseases.
Apoptosis, also known as activation-induced cell death or programmed cell death, is an active suicide mechanism that is involved in normal tissue turnover during embryogenesis and adult life. There are many examples of apoptosis in the immune system, including programmed cell death of T cells during negative intrathymic selection of the TCR repertoire and, in the postthymic phase, death of responsive T cells upon specific activation of the TCR/CD3 complex. Induction of apoptosis assures rapid disappearance of the immune response upon antigenic clearance, avoiding the metabolic costs involved in sustaining a large number of effector cells. The knowledge that failure of immune cells to die is the cause of a number of immune-mediated disorders has opened intriguing new avenues of exploration into the pathogenetic events leading to the accumulation of immunoinflammatory cells at sites of ongoing inflammation in granulomatous disorders, including granulomas initiated by infectious agents, such as Mycobacterium tuberculosis, or in sarcoidosis. In this paper we review recent results obtained in experimental animal models and patients with immune granuloma suggesting that the positive induction by ligands binding to membrane receptors or the induction or loss of intracellular suppressor signals regulates immunoregulatory mechanisms that drive the progressive development of the granulomatous structure. The great advances in understanding how mechanisms for the activation or downregulation of apoptosis have a pathogenetic role in the outcome of granulomatous disorders are also briefly considered.
Agostini
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Dipartimento di Medicina Clinica e Sperimentale, Università di Padova, Immunologia Clinica, Italy.
Perin
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Semenzato
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D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000276:immunology / Q000502:physiology*; D017252:CD3 Complex / Q000276:immunology; D004195:Disease Models, Animal; D015536:Down-Regulation; D006099:Granuloma / Q000209:etiology* / Q000276:immunology; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000209:etiology* / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D017565:Sarcoidosis, Pulmonary / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D014375:Tuberculoma / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology
D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell