SOCS-1 regulates IL-15-driven homeostatic proliferation of antigen-naive CD8 T cells, limiting their autoimmune potential
AuthorDavey, GM; Starr, R; Cornish, AL; Burghardt, JT; Alexander, WS; Carbone, FR; Surh, CD; Heath, WR
Source TitleJOURNAL OF EXPERIMENTAL MEDICINE
PublisherROCKEFELLER UNIV PRESS
AffiliationMicrobiology and Immunology
Research, Innovation and Commercialisation
Document TypeJournal Article
CitationsDavey, 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.
Access StatusOpen Access
Mice 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.
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