HLA-DP4 expression and immunity to NY-ESO-1: Correlation and characterization of cytotoxic CD4+ CD25- CD8- T cell clones Journal Article
| Authors: | Huarte, E.; Karbach, J.; Gnjatic, S.; Bender, A.; Jäger, D.; Arand, M.; Atanackovic, D.; Skipper, J.; Ritter, G.; Chen, Y. T.; Old, L. J.; Knuth, A.; Jäger, E. |
| Article Title: | HLA-DP4 expression and immunity to NY-ESO-1: Correlation and characterization of cytotoxic CD4+ CD25- CD8- T cell clones |
| Abstract: | NY-ESO-1 is one of the most immunogenic cancer antigens known to date, eliciting spontaneous immune responses in approximately 50% of patients with NY-ESO-1+ cancers. Spontaneous CD4+ and CD8+ T cell responses were found in patients with detectable NY-ESO-1 serum antibody, indicating an integrated type of immune response induced by NY-ESO-1+ malignancies. A close association between spontaneous NY-ESO-1 immunity and the HLA-DP4 allele was suggested in a recent study. To address these results, we assessed the NY-ESO-1 antibody and HLA-DP4 status of 102 patients with NY-ESO-1+ malignancies. However, no correlation between HLA-DP4 and NY-ESO-1 immunity was found. To explore the role of HLA-DP4-restricted CD4+ T cells in cancer immunity, we established HLA-DP4-restricted NY-ESO-1-specific CD4+ T cell clones by limiting dilution and repeated stimulation with NY-ESO-1 peptide p157-170 from NY-ESO-1 seropositive patients. A subset of CD4+ T cell clones was reactive with naturally processed NY-ESO-1 presented by autologous DCs that were pulsed with recombinant NY-ESO-1 protein, lysates of NY-ESO-1-expressing tumor cell lines, or transduced with recombinant NY-ESO-1 viral constructs in ELISPOT assays. Three different CD4+ T cell clones were used to mediate the specific lysis of allogeneic HLA-DP4+ Epstein-Barr virus-transformed B cells (EBV-B) pulsed with NY-ESO-1 p157-170. The Th1 phenotype and effector functions of the CD4+ T cell clones described here provide an important rationale for the activation of antigen-specific CD4+ T cells along with CD8+ T cells in cancer vaccination strategies. |
| Keywords: | controlled study; human tissue; protein expression; unclassified drug; human cell; major clinical study; cd8 antigen; antigen expression; tumor antigen; correlation analysis; immune response; ny eso 1 antigen; cytotoxic t lymphocyte; tumor immunity; immunophenotyping; cd4 antigen; humoral immunity; interleukin 2 receptor alpha; ny-eso-1; cell cloning; hla-dp4; hla dp4 antigen; cancer; human; article; cytotoxic t cells |
| Journal Title: | Cancer Immunity |
| Volume: | 4 |
| ISSN: | 1424-9634 |
| Publisher: | Academy of Cancer Immunology |
| Date Published: | 2004-12-16 |
| Start Page: | 15 |
| End Page: | 21 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 15600300 |
| DOI/URL: | |
| Notes: | Cancer Immun. -- Cited By (since 1996):2 -- Export Date: 16 June 2014 -- Source: Scopus |
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