title: Characterization of antigen-specific CD8+ T lymphocyte responses in skin and peripheral blood following intradermal peptide vaccination.
abstract: Immune responses to cancer vaccines are commonly tested by measuring cutaneous reactions to intradermal (i.d.) antigen. When well-characterized peptide epitopes are injected i.d., infiltrates of CD4+ and CD8+ T lymphocytes are frequently seen. In this study, we have further characterized T cells derived from vaccine-infiltrating lymphocyte (VIL) responses. We found that the infiltrates capable of producing IFN-gamma and cytolytic activity could recognize vaccine peptide, as well as antigen-positive melanoma cells. We studied antigen-specific T cell responses from VILs and peripheral blood in 10 patients who participated in a clinical trial. All patients received systemic Flt3 ligand (20 microg/kg/d) and i.d. peptides: Three NY-ESO-1 peptides, SLLMWITQCFL (157-167), SLLMWITQC (157-165), QLSLLMWIT (155-163); tyrosinase internal peptide YMDGTMSQV (368-376); Melan-A/MART-1 analogue peptide ELAGIGILTV (26-35, E27L substitution); and influenza matrix peptide GILGFVFTL (58-66). In 54 paired VIL and peripheral blood analyses, a good correlation was found between responses in skin and in blood. These cells could be rapidly expanded in a short-term assay and thus appear to be memory T cells. The demonstrated presence of antigen-specific T cells at vaccination sites validates this method of assessing the immune response to i.d. vaccines.
authors.affiliation: Ludwig Institute for Cancer Research, Heidelberg, Victoria, Australia.
authors.forename: Qiyuan
authors.initials: Q
authors.lastname: Chen
authors.forename: Heather
authors.initials: H
authors.lastname: Jackson
authors.forename: Mark
authors.initials: M
authors.lastname: Shackleton
authors.forename: Phillip
authors.initials: P
authors.lastname: Parente
authors.forename: Wendie
authors.initials: W
authors.lastname: Hopkins
authors.forename: Sue
authors.initials: S
authors.lastname: Sturrock
authors.forename: Duncan
authors.initials: D
authors.lastname: MacGregor
authors.forename: Eugene
authors.initials: E
authors.lastname: Maraskovsky
authors.forename: Tsin Yee
authors.initials: TY
authors.lastname: Tai
authors.forename: Nektaria
authors.initials: N
authors.lastname: Dimopoulos
authors.forename: Kelly-Anne
authors.initials: KA
authors.lastname: Masterman
authors.forename: Tina
authors.initials: T
authors.lastname: Luke
authors.forename: Ian D
authors.initials: ID
authors.lastname: Davis
authors.forename: Weisan
authors.initials: W
authors.lastname: Chen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cebon
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D001773:Blood Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000096:biosynthesis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008545:Melanoma / Q000276:immunology; D012867:Skin / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D022223:Vaccines, Subunit; D007371:Interferon-gamma