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: Qiyuan Chen, Heather Jackson, Mark Shackleton, Phillip Parente, Wendie Hopkins, Sue Sturrock, Duncan MacGregor, Eugene Maraskovsky, Tsin Yee Tai, Nektaria Dimopoulos, Kelly-Anne Masterman, Tina Luke, Ian D Davis, Weisan Chen, Jonathan Cebon
• Journal: Cancer immunity (Cancer Immun) Vol. 5 Pg. 5 (Mar 09 2005) ISSN: 1424-9634 [Electronic] United States
• PMID: 15755075 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Cancer Vaccines
• Vaccines, Subunit
• Interferon-gamma

Topics

• Antigens, Neoplasm (immunology)
• Blood Cells (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (administration & dosage, immunology)
• Cell Line, Tumor
• Cytotoxicity Tests, Immunologic
• Humans
• Hypersensitivity, Delayed (immunology)
• Injections, Intradermal
• Interferon-gamma (biosynthesis)
• Lymphocytes, Tumor-Infiltrating (immunology)
• Melanoma (immunology)
• Skin (immunology)
• Skin Neoplasms (immunology)
• Vaccines, Subunit (administration & dosage, immunology)