FAS CD95-MEDIATED APOPTOSIS IN THE PATHOG ENESIS OF LYMPHOID NEOPLASMS/

Apoptosis is a critical feature of the development of multicellular or ganisms. CD95-mediated apoptosis plays important roles in the immune h omeostasis: maintaining of peripheral tolerance, downregulation of imm une reactions via the elimination of activated lymphocytes after they have responded to foreign antigens, and mediating T cell cytotoxicity. CD95 is a member of TNF/NGF receptor superfamily and exists in transm embrane and soluble forms. Malfunction of CD95 system causes lymphopro liferative disorders and accelerates autoimmune diseases. The review s ummarizes recent data on intracellular pathways leading from membrane CD95 receptor engagement to apoptotic cell death, modulation of CD95 e xpression and function via antigen receptors and coreceptor molecules on T and B lymphocytes. CD95 plays a dual role showing the ability to mediate either stimulatory or apoptotic signals depending on the stage of lymphocyte differentiation and activation. Expression and function CD95 on malignant cells at leukemias and lymphomas is of diagnostic s ignificance and also is involved in pathogenesis of neoplasms. Knowled ge of the ways for CD95 modulation on the surface of normal and neopla stic lymphocytes will open a new approaches to immunotherapy of leukem ias and lymphomas.