title: Apoptosis induced in HIV-1-exposed, resting CD4+ T cells subsequent to signaling through homing receptors is Fas/Fas ligand-mediated.
abstract: The hallmark of HIV-1 disease is the gradual disappearance of CD4+ T cells from the blood. The mechanism of this depletion, however, is still unclear. Evidence suggests that lymphocytes die in lymph nodes, not in blood, and that uninfected bystander cells are the predominant cells dying. Our and others' previous studies showed that the lymph node homing receptor, CD62 ligand (CD62L), and Fas are up-regulated on resting CD4+ T cells after HIV-1 binding and that these cells home to lymph nodes at an enhanced rate. During the homing process, signals are induced through various homing receptors, which in turn, induced many of the cells to undergo apoptosis after they entered the lymph nodes. The purpose of this study was to determine how the homing process induces apoptosis in HIV-1-exposed, resting CD4+ T cells. We found that signaling through CD62L up-regulated FasL. This resulted in apoptosis of only HIV-1-presignaled, resting CD4+ T cells, not normal CD4+ T cells. This homing receptor-induced apoptosis could be blocked by anti-FasL antibodies or soluble Fas, demonstrating that the Fas-FasL interaction caused the apoptotic event.
authors.affiliation: Department of Microbiology and Immunology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555-1070, USA.
authors.forename: Jiaxiang
authors.initials: J
authors.lastname: Ji
authors.forename: Jenny J-Y
authors.initials: JJ
authors.lastname: Chen
authors.forename: Vivian L
authors.initials: VL
authors.lastname: Braciale
authors.forename: Miles W
authors.initials: MW
authors.lastname: Cloyd
mesh_terms: D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000821:virology*; D002478:Cells, Cultured; D015536:Down-Regulation; D019040:E-Selectin / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D019040:E-Selectin; D053222:Fas Ligand Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor