title: CD70 deficiency impairs effector CD8 T cell generation and viral clearance but is dispensable for the recall response to lymphocytic choriomeningitis virus.
abstract: CD27 interactions with its ligand, CD70, are thought to be necessary for optimal primary and memory adaptive immune responses to a variety of pathogens. Thus far, all studies addressing the function of the CD27-CD70 axis have been performed in mice lacking CD27, in those overexpressing CD70, or in those in which these molecules were blocked or mimicked by Abs or recombinant soluble CD70. Because these methods have in some cases led to divergent results, we generated CD70-deficient mice to directly assess its role in vivo. We find that lack of CD70-mediated stimulation during primary responses to lymphocytic choriomeningitis virus lowered the magnitude of CD8 Ag-specific T cell response, resulting in impaired viral clearance, without affecting CD4 T cell responses. Unexpectedly, CD70-CD27 costimulation was not needed for memory CD8 T cell generation or the ability to mount a recall response to lymphocytic choriomeningitis virus. Adoptive transfers of wild-type memory T cells into CD70(-/-) or wild-type hosts also showed no need for CD70-mediated stimulation during the course of the recall response. Moreover, CD70 expression by CD8 T cells could not rescue endogenous CD70(-/-) cells from defective expansion, arguing against a role for CD70-mediated T:T help in this model. Therefore, CD70 appears to be an important factor in the initiation of a robust and effective primary response but dispensable for CD8 T cell memory responses.
authors.affiliation: Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ivana
authors.initials: I
authors.lastname: Munitic
authors.forename: Mirela
authors.initials: M
authors.lastname: Kuka
authors.forename: Atef
authors.initials: A
authors.lastname: Allam
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Scoville
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Ashwell
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D053282:CD27 Ligand / Q000172:deficiency* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D000939:Epitopes / Q000276:immunology; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology / Q000302:isolation & purification; D008222:Lymphokines / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000276:immunology / Q000821:virology; D037182:T-Cell Antigen Receptor Specificity; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology; D019562:Viral Load
chemical_list: D000956:Antigens, Viral; D053282:CD27 Ligand; D000939:Epitopes; D008222:Lymphokines; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7