Characterization of antigen-specific CD8+ T lymphocyte responses in skin and peripheral blood following intradermal peptide vaccination.
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.
Chen
Qiyuan
Q
Ludwig Institute for Cancer Research, Heidelberg, Victoria, Australia.
Jackson
Heather
H
Shackleton
Mark
M
Parente
Phillip
P
Hopkins
Wendie
W
Sturrock
Sue
S
MacGregor
Duncan
D
Maraskovsky
Eugene
E
Tai
Tsin Yee
TY
Dimopoulos
Nektaria
N
Masterman
Kelly-Anne
KA
Luke
Tina
T
Davis
Ian D
ID
Chen
Weisan
W
Cebon
Jonathan
J
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
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D022223:Vaccines, Subunit; D007371:Interferon-gamma