Characterization of preexisting MAGE-A3-specific CD4(+) T cells in cancer patients and healthy individuals and their activation by protein vaccination Journal Article
| Authors: | Tsuji, T.; Altorki, N. K.; Ritter, G.; Old, L. J.; Gnjatic, S. |
| Article Title: | Characterization of preexisting MAGE-A3-specific CD4(+) T cells in cancer patients and healthy individuals and their activation by protein vaccination |
| Abstract: | Vaccination with cancer/testis Ag MAGE-A3 in the form of recombinant protein often induces specific humoral and cellular immune responses. Although Ag-specific CD4(+) T cells following vaccination are detectable by cytokine production after a single in vitro stimulation, their detection before vaccination is difficult because of low frequency. In this study, we have applied a sensitive method using CD154 (CD40L) staining to detect MAGE-A3-specific CD4(+) T cells. MAGE-A3-specific T cell responses were analyzed in four healthy donors, two lung cancer patients with spontaneous serum Abs to MAGE-A3, and two baseline seronegative lung cancer patients throughout vaccination with MAGE-A3 protein. MAGE-A3-specific CD4(+) T cells were detected in all individuals tested, at low frequency in healthy donors and seronegative cancer patients and higher frequency in patients seropositive for MAGE-A3. Polyclonal expansion of CD154-expressing CD4 (+) T cells after cell sorting generated a large number of MAGE-A3-specific CD4(+) T cell lines from all individuals tested, enabling full characterization of peptide specificity, HLA-restriction, and avidity. Application of this method to cancer patients vaccinated with MAGE-A3 protein with or without adjuvant revealed that protein vaccination induced oligoclonal activation of MAGE-A3-specific CD4(+) T cells. It appeared that MAGE-A3 protein vaccination in the presence of adjuvant selectively expanded high avidity CD4(+) T cells, whereas high avidity T cells disappeared after multiple vaccinations with MAGE-A3 protein alone. Copyright © 2009 by The American Association of Immunologists, Inc. |
| Keywords: | controlled study; human cell; adjuvant therapy; cancer patient; comparative study; binding affinity; cytology; lung non small cell cancer; carcinoma, non-small-cell lung; lung neoplasms; cd40 ligand; neoplasm proteins; cell line; protein binding; lung cancer; pathology; tumor cell culture; tumor cells, cultured; tumor antigen; time; time factors; cell specificity; lung tumor; immunology; lymphocyte activation; antigens, neoplasm; cancer vaccine; cancer vaccines; antigen specificity; melanoma antigen 3; cancer immunization; cd4+ t lymphocyte; cd4-positive t-lymphocytes; epitope; tumor protein; cell line, transformed; immunological adjuvant; cd4 lymphocyte count; adjuvants, immunologic; epitopes, t-lymphocyte; t lymphocyte activation; vaccines, subunit; cell selection; hla system; immunization; oligoclonal band; magea3 protein, human; subunit vaccine; protein vaccination; coculture; coculture techniques; immunization, secondary |
| Journal Title: | Journal of Immunology |
| Volume: | 183 |
| Issue: | 7 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2009-10-01 |
| Start Page: | 4800 |
| End Page: | 4808 |
| Language: | English |
| DOI: | 10.4049/jimmunol.0900903 |
| PUBMED: | 19734225 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 30 November 2010" - "CODEN: JOIMA" - "Source: Scopus" |
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