Viral regulation of CD95 expression and apoptosis in T lymphocytes.
T lymphocyte apoptosis has been observed in vivo in association with viral infections. One mechanism known to mediate T cell apoptosis is the CD95 (Fas/APO-1) Ag apoptotic pathway. CD95 is a cell surface protein that is expressed on activated T cells and is capable of relaying an intracellular apoptotic signal upon binding with CD95 ligand. CD95-dependent apoptosis has been shown to be involved in the homeostatic control of peripheral T cell numbers; however, the functional significance of the CD95 apoptotic pathway in the context of viral infections has not been clearly elucidated. We show that exposure to a variety of viral pathogens causes enhanced CD95 expression in naive peripheral blood cell T lymphocytes without leading to enhanced susceptibility to CD95-dependent apoptosis. Productive viral infection was not required for this effect. Furthermore, using a T cell line and the K562 tumor cell line, we demonstrate that cells normally resistant to CD95-mediated killing become susceptible when productively infected with virus in a manner that does not rely on increased CD95 surface expression. These findings demonstrate a regulatory influence of viral infection on CD95 expression and activity and suggest that in addition to having a role in T cell homeostasis, the CD95 apoptotic pathway might also function to eliminate virus-infected T cells.
Sieg
S
S
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Huang
Y
Y
Kaplan
D
D
D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004789:Enzyme Activation; D018259:Herpesvirus 1, Human / Q000502:physiology; D018258:Herpesvirus 2, Human / Q000502:physiology; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D010224:Parainfluenza Virus 3, Human / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000821:virology*; D014407:Tumor Cells, Cultured; D018406:Virus Physiological Phenomena; D019014:fas Receptor / Q000096:biosynthesis*
D019014:fas Receptor; D011505:Protein-Tyrosine Kinases