TY - JOUR AU - Davey, GM AU - Starr, R AU - Cornish, AL AU - Burghardt, JT AU - Alexander, WS AU - Carbone, FR AU - Surh, CD AU - Heath, WR Y2 - 2020/09/18 Y1 - 2005/10/17 SN - 0022-1007 UR - http://hdl.handle.net/11343/242534 AB - 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. LA - English PB - ROCKEFELLER UNIV PRESS T1 - SOCS-1 regulates IL-15-driven homeostatic proliferation of antigen-naive CD8 T cells, limiting their autoimmune potential DO - 10.1084/jem.20050003 IS - JOURNAL OF EXPERIMENTAL MEDICINE VL - 202 IS - 8 SP - 1099-1108 L1 - /bitstream/handle/11343/242534/PMC2213211.pdf?sequence=1&isAllowed=y ER -