Neonatal Tolerance Revisited: A Perinatal Window for Aire Control of Autoimmunity

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Neonatal Tolerance Revisited: A Perinatal Window for Aire Control of Autoimmunity

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dc.contributor.author Guerau-de-Arellano, Mireia
dc.contributor.author Martinic, Marianne
dc.contributor.author Benoist, Christophe O.
dc.contributor.author Mathis, Diane J.
dc.date.accessioned 2012-03-11T00:41:47Z
dc.date.issued 2009
dc.identifier.citation Guerau-de-Arellano, Mireia, Marianne Martinic, Christophe Benoist, and Diane Mathis. 2009. Neonatal tolerance revisited: a perinatal window for Aire control of autoimmunity. The Journal of Experimental Medicine 206(6): 1245-1252. en_US
dc.identifier.issn 0022-1007 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:8347343
dc.description.abstract There has long been conceptual and experimental support for, but also challenges to, the notion that the initial period of the immune system's development is particularly important for the establishment of tolerance to self. The display of self-antigens by thymic epithelial cells is key to inducing tolerance in the T lymphocyte compartment, a process enhanced by the Aire transcription factor. Using a doxycycline-regulated transgene to target Aire expression to the thymic epithelium, complementing the Aire knockout in a temporally controlled manner, we find that Aire is essential in the perinatal period to prevent the multiorgan autoimmunity that is typical of Aire deficiency. Surprisingly, Aire could be shut down soon thereafter and remain off for long periods, with few deleterious consequences. The lymphopenic state present in neonates was a factor in this dichotomy because inducing lymphopenia during Aire turnoff in adults recreated the disease, which, conversely, could be ameliorated by supplementing neonates with adult lymphocytes. In short, Aire expression during the perinatal period is both necessary and sufficient to induce long-lasting tolerance and avoid autoimmunity. Aire-controlled mechanisms of central tolerance are largely dispensable in the adult, as a previously tolerized T cell pool can buffer newly generated autoreactive T cells that might emerge. en_US
dc.language.iso en_US en_US
dc.publisher The Rockefeller University Press en_US
dc.relation.isversionof doi:10.1084/jem.20090300 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715060/pdf/ en_US
dash.license LAA
dc.title Neonatal Tolerance Revisited: A Perinatal Window for Aire Control of Autoimmunity en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal The Journal of Experimental Medicine en_US
dash.depositing.author Mathis, Diane J.
dc.date.available 2012-03-11T00:41:47Z
dash.affiliation.other HMS^Pathology en_US
dash.affiliation.other HMS^Pathology en_US

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