title: Antiapoptotic Role for Lifeguard in T Cell Mediated Immune Response.
abstract: Anti-apoptotic protein Lifeguard (LFG) is upregulated on T cells upon in vitro activation. To investigate its role in T cell immunity we infected wild type and LFG knockout bone marrow chimaeras mice with LCMV. We observed a decreased number of LFG KO activated CD8 and CD4 T cells throughout the infection and a marked decrease in LFG KO LCMV specific memory T cells. WT and KO T cells proliferated at the same rate, however, LFG KO CD44(hi) T cells showed increased cell death during the initial phase of the immune response. LFG KO and WT T cells were equally sensitive to the FAS antibody Jo-2 in ex vivo cultures, and blocking extrinsic pathways of cell death in vivo with Fas L or caspase 8 inhibitors did not rescue the increased apoptosis in LFG KO T cells. Our data suggest that LFG plays a role in T cell survival during the initial phase of anti-viral immune response by protecting pre-existing memory T cells and possibly newly activated T cells resulting in a diminished immune response and a decreased number of LCMV specific memory T cells.
authors.affiliation: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California, United States of America.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Hurtado de Mendoza
authors.affiliation: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California, United States of America.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California, United States of America.
authors.forename: Inder M
authors.initials: IM
authors.lastname: Verma
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D007111:Immunity, Cellular; D008213:Lymphocyte Activation; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000302:isolation & purification; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D019014:fas Receptor / Q000276:immunology
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019014:fas Receptor; C523971:lifeguard protein, mouse