ANTIINFLAMMATORY EFFECTS OF CD95 LIGAND (FASL)-INDUCED APOPTOSIS

Apoptosis is critical to homeostasis of multicellular organisms. In im mune privileged sites such as the eye, CD95 ligand (FasL)-induced apop tosis controls dangerous inflammatory reactions that can cause blindne ss. Recently, we demonstrated that apoptotic cell death of inflammator y cells was a prerequisite for the induction of immune deviation after antigen presentation in the eye. In this report, we examine the mecha nism by which this takes place. Our results show that Fas-mediated apo ptosis of lymphoid cells leads to rapid production of interleukin (IL) -10 in these cells. The apoptotic cells containing IL-10 are responsib le for the activation of immune deviation through interaction with ant igen-presenting cells (APC). In support of this, we found that apoptot ic cells from IL-10(+/+) animals fed to APC in vitro promote Th2 cell differentiation, whereas apoptotic IL-10(-/-) cells, as well as nonapo ptotic cells, favor Th1 induction. Thus, apoptotic cell death and tole rance are linked through the production of an antiinflammatory cytokin e to prevent dangerous and unwanted immune responses that might compro mise organ integrity.