title: Thymocyte death by neglect: contribution of engulfing macrophages.
abstract: The thymus provides the microenvironment in which thymocytes develop into mature T cells, and interactions with thymic stromal cells are thought to provide the necessary signals for thymocyte maturation. Recognition of self-MHC by T cells is a basic requirement for mature T-cell functions, and those thymocytes that do not recognize the peptide-loaded self-MHC molecules found in the thymus, and therefore lack a TCR signal, undergo a default death pathway named "death by neglect" in the thymic cortex. In the absence of this TCR signaling, it has been suggested that binding of glucocorticoids to - or the ligation of certain cell surface molecules, such as CD8, CD24, CD45, or CD99 on - these neglected thymocytes will induce them to enter the apoptotic program. Apoptotic thymocytes are cleared by the surrounding macrophages and, as a consequence, these macrophages are known to release various molecules, such as adenosine, retinoids, TGF-β, ATP, and carbon monoxide. Interestingly, all these molecules have been described to induce or promote apoptosis in thymocytes in the absence of TCR signaling. Here, we propose that thymic macrophages, because they continually engulf apoptotic cells, might constantly provide these cell death-inducing signals, and thus contribute to the formation of a thymic milieu that ensures the effective induction of "death by neglect".
authors.affiliation: Department of Biochemistry and Molecular Biology, Apoptosis and Genomics Research Group of the Hungarian Academy of Sciences, Research Center of Molecular Medicine, University of Debrecen, Debrecen, Hungary. szondy@dote.hu
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Szondy
authors.forename: Éva
authors.initials: É
authors.lastname: Garabuczi
authors.forename: Katalin
authors.initials: K
authors.lastname: Tóth
authors.forename: Bea
authors.initials: B
authors.lastname: Kiss
authors.forename: Krisztina
authors.initials: K
authors.lastname: Köröskényi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000276:immunology; D060168:Thymocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology