Characterization of Preexisting MAGE-A3-Specific CD4+ T Cells in Cancer Patients and Healthy Individuals and Their Activation by Protein Vaccination

  • Tsuji T
  • Altorki N
  • Ritter G
  • et al.
30Citations
Citations of this article
38Readers
Mendeley users who have this article in their library.

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.

Cite

CITATION STYLE

APA

Tsuji, T., Altorki, N. K., Ritter, G., Old, L. J., & Gnjatic, S. (2009). Characterization of Preexisting MAGE-A3-Specific CD4+ T Cells in Cancer Patients and Healthy Individuals and Their Activation by Protein Vaccination. The Journal of Immunology, 183(7), 4800–4808. https://doi.org/10.4049/jimmunol.0900903

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free