title: Late signals from CD27 prevent Fas-dependent apoptosis of primary CD8+ T cells.
abstract: The role of costimulation has previously been confined to the very early stages of the CD8+ T cell response. In this study, we demonstrate the requirement for CD27 costimulation during the later phase, but not programming of the primary CD8+ T cell response to influenza virus and reveal a novel mechanism of action for CD27 costimulation. CD27 signals, during the later phase of the primary CD8+ T cell response, prevent apoptosis of Ag-specific CD8+ T cells. Blocking CD27L (CD70) on days 6 and 8 after infection reduces the number of NP(366-374)-specific CD8+ T cells, increases their sensitivity to CD95/Fas-mediated apoptosis, and up-regulates FasL on CD4+ T cells. This reduction of NP(366-374)-specific CD8+ T cells requires the presence of CD4+ T cells and Fas signaling. Lack of CD27 signals also decreases the quality of memory CD8+ T cell responses. Memory CD8+ T cells, which express surface CD27 similar to naive cells, however, do not require CD27 costimulation during a secondary response. Thus, CD27 acts indirectly to regulate primary Ag-specific CD8+ T cell responses by preventing apoptosis of CD8+ T cells during the later phase of the primary response and is required for optimal quality of memory cells, but is not required during normally primed secondary CD8+ T cell responses.
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
authors.forename: Douglas V
authors.initials: DV
authors.lastname: Dolfi
authors.forename: Alina C
authors.initials: AC
authors.lastname: Boesteanu
authors.forename: Constantinos
authors.initials: C
authors.lastname: Petrovas
authors.forename: Dong
authors.initials: D
authors.lastname: Xia
authors.forename: Eric A
authors.initials: EA
authors.lastname: Butz
authors.forename: Peter D
authors.initials: PD
authors.lastname: Katsikis
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D019138:Antibodies, Blocking / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D053282:CD27 Ligand / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation / Q000821:virology; D007117:Immunization, Secondary; D007156:Immunologic Memory / Q000235:genetics; D009980:Influenza A virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013997:Time Factors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014758:Viral Core Proteins / Q000008:administration & dosage / Q000276:immunology; D019014:fas Receptor / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D053282:CD27 Ligand; C505772:Cd70 protein, mouse; D010446:Peptide Fragments; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014758:Viral Core Proteins; D019014:fas Receptor; C102366:nucleoprotein (366-374), influenza virus