In vivo analysis of Fas antigen-mediated apoptosis: Effects of agonistic anti-mouse Fas mAb on thymus, spleen and liver

Fas antigen (Fas/CD95) is a cell surface receptor protein that mediates apoptosis-inducing signals, To analyze the function of Fas in vivo, we examined the effects of agonistic anti-Fas antibodies in mice. The i.p. administration of the hamster anti-mouse Fas mAb, RK-8, which induced apoptosis both in vivo and in vitro, did not kill adult mice, whereas those given the another hamster anti-mouse Fas mAb, Jo2, rapidly died of fulminant hepatitis with hemorrhage. Histological analyses of mice given RK-8 indicated severe damage of the thymus, and moderate damage of the spleen and liver, Most of the thymocytes and some hepatocytes underwent apoptosis within 1 day of administration, Flow cytometry revealed that CD4(+) T cells were more sensitive to Fas-mediated apoptosis than CD8(+) T cells, At day 7 after administration, the thymus was atrophied, These in vivo effects of RK-8 were transient; the thymus was regenerated, and the liver and spleen were apparently normal 1 month after injection, The administration of RK-8 into newborn mice caused severe damage of the liver and thymus, Most of the hepatocytes died and jaundice was induced, The newborn mice died within 1 week, Most hepatocytes of newborn mice may be more sensitive to apoptosis-inducing signals through Fas than those of adult mice, These results indicated that functional Fas, which introduces the death signal in vivo, is expressed on thymocytes, CD4(+) splenocytes, and some adult and most newborn mouse hepatocytes.