The role of the antigen-presenting cell in Fas-mediated direct and bystander killing: Potential in vivo function of fas in experimental allergic encephalomyelitis

Anja R.B. Thilenius, Kimberly A. Sabelko-Downes, John H. Russell

Research output: Contribution to journalArticle

32 Scopus citations

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.

Original languageEnglish
Pages (from-to)643-650
Number of pages8
JournalJournal of Immunology
Volume162
Issue number2
StatePublished - Jan 15 1999

Fingerprint Dive into the research topics of 'The role of the antigen-presenting cell in Fas-mediated direct and bystander killing: Potential in vivo function of fas in experimental allergic encephalomyelitis'. Together they form a unique fingerprint.

  • Cite this