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dc.contributor.authorDavey, GM
dc.contributor.authorStarr, R
dc.contributor.authorCornish, AL
dc.contributor.authorBurghardt, JT
dc.contributor.authorAlexander, WS
dc.contributor.authorCarbone, FR
dc.contributor.authorSurh, CD
dc.contributor.authorHeath, WR
dc.date.accessioned2020-09-18T03:55:45Z
dc.date.available2020-09-18T03:55:45Z
dc.date.issued2005-10-17
dc.identifierpii: jem.20050003
dc.identifier.citationDavey, G. M., Starr, R., Cornish, A. L., Burghardt, J. T., Alexander, W. S., Carbone, F. R., Surh, C. D. & Heath, W. R. (2005). SOCS-1 regulates IL-15-driven homeostatic proliferation of antigen-naive CD8 T cells, limiting their autoimmune potential. JOURNAL OF EXPERIMENTAL MEDICINE, 202 (8), pp.1099-1108. https://doi.org/10.1084/jem.20050003.
dc.identifier.issn0022-1007
dc.identifier.urihttp://hdl.handle.net/11343/242534
dc.description.abstractMice that are deficient in suppressor of cytokine signaling-1 (SOCS-1) succumb to neonatal mortality that is associated with extensive cellular infiltration of many tissues. T cells seem to be necessary for disease, which can be alleviated largely by neutralizing interferon-gamma. Examining T cell receptor (TCR) specificity shows that even monospecific T cells can mediate disease in SOCS-1-deficient mice, although disease onset is substantially faster with a polyclonal T cell repertoire. A major phenotype of SOCS-1-/- mice is the accumulation of CD44(high)CD8+ peripheral T cells. We show that SOCS-1-deficient CD8, but not CD4, T cells proliferate when transferred into normal (T cell-sufficient) mice, and that this is dependent on two signals: interleukin (IL)-15 and self-ligands that are usually only capable of stimulating homeostatic expansion in T cell-deficient mice. Our findings reveal that SOCS-1 normally down-regulates the capacity of IL-15 to drive activation and proliferation of naive CD8 T cells receiving TCR survival signals from self-ligands. We show that such dysregulated proliferation impairs the deletion of a highly autoreactive subset of CD8 T cells, and increases their potential for autoimmunity. Therefore, impaired deletion of highly autoreactive CD8 T cells, together with uncontrolled activation of naive CD8 T cells by homeostatic survival ligands, may provide a basis for the T cell-mediated disease of SOCS-1-/- mice.
dc.languageEnglish
dc.publisherROCKEFELLER UNIV PRESS
dc.titleSOCS-1 regulates IL-15-driven homeostatic proliferation of antigen-naive CD8 T cells, limiting their autoimmune potential
dc.typeJournal Article
dc.identifier.doi10.1084/jem.20050003
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.affiliation.departmentResearch, Innovation and Commercialisation
melbourne.source.titleJOURNAL OF EXPERIMENTAL MEDICINE
melbourne.source.volume202
melbourne.source.issue8
melbourne.source.pages1099-1108
dc.rights.licenseCC BY-NC-SA
melbourne.elementsid270207
melbourne.contributor.authorDavey, Gayle
melbourne.contributor.authorCarbone, Francis
melbourne.contributor.authorHeath, William
melbourne.contributor.authorCornish, Ann
dc.identifier.eissn1540-9538
melbourne.accessrightsOpen Access


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