The role of the antigen-presenting cell in Fas-mediated direct and bystander killing: potential in vivo function of Fas in experimental allergic encephalomyelitis
ARB Thilenius, KA Sabelko-Downes… - The Journal of …, 1999 - journals.aai.org
ARB Thilenius, KA Sabelko-Downes, JH Russell
The Journal of Immunology, 1999•journals.aai.orgCostimulatory molecules are critical in mediating Fas-dependent direct and bystander lysis.
In direct lysis, the APC is the Fas-positive target. It presents Ag to the T cell, thereby
activating the T cell. The activated T cell then up-regulates FasL, allowing it to kill the APC. In
bystander lysis, the APC again induces FasL expression on the T cell, but the target is a third
Fas-positive cell that may lack the appropriate MHC-restricting element to activate the T cell.
This study shows that ICAM-1 and B7-1 can serve as important adhesion molecules in direct …
In direct lysis, the APC is the Fas-positive target. It presents Ag to the T cell, thereby
activating the T cell. The activated T cell then up-regulates FasL, allowing it to kill the APC. In
bystander lysis, the APC again induces FasL expression on the T cell, but the target is a third
Fas-positive cell that may lack the appropriate MHC-restricting element to activate the T cell.
This study shows that ICAM-1 and B7-1 can serve as important adhesion molecules in direct …
Abstract
Costimulatory molecules are critical in mediating Fas-dependent direct and bystander lysis. In direct lysis, the APC is the Fas-positive target. It presents Ag to the T cell, thereby activating the T cell. The activated T cell then up-regulates FasL, allowing it to kill the APC. In bystander lysis, the APC again induces FasL expression on the T cell, but the target is a third Fas-positive cell that may lack the appropriate MHC-restricting element to activate the T cell. This study shows that ICAM-1 and B7-1 can serve as important adhesion molecules in direct killing using CD4+ T cell effectors. In bystander killing, B7-1 appears to act as a signaling molecule as well. It has been demonstrated that lpr and gld mice are less susceptible to experimental allergic encephalomyelitis than their wild-type counterparts. In this study, we show that although microglia are poor targets of direct killing, they are capable of stimulating myelin basic protein-specific T cells to kill innocent Fas-positive targets. This presents a possible mechanism for the pathogenesis of experimental allergic encephalomyelitis.
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