Spontaneous proliferation and type 2 cytokine secretion by CD4+T cells in patients with metastatic melanoma vaccinated with antigen-pulsed dendritic cells

A. Karolina Palucka, John Connolly, Hideki Ueno, John Kohl, Sophie Paczesny, Madhav Dhodapkar, Joseph Fay, Jacques Banchereau

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

We observed the induction of spontaneous, i.e., without adding exogenous antigen, in vitro proliferation of PBMCs from patients with stage IV melanoma who underwent repeated vaccinations with antigen-loaded dendritic cells (DCs) derived from CD34+ hematopoietic progenitors (CD34-DCs). Proliferating cells are CD4+T cells. Their proliferation is dependent on (1) CD11c+ myeloid DCs, since their depletion from PBMCs abolishes it; and (2) IL-2, as it can be blocked by neutralizing anti-IL-2 antibodies. Spontaneous proliferation is associated to the secretion of type 2 cytokines. To analyze the frequency of spontaneous proliferation induction in the cohort of 18 vaccinated patients, an index of spontaneous proliferation was defined as a ratio of PBMCs proliferation from post- vs pre-DC vaccination blood samples. Ten out of sixteen analyzed patients showed an index >2. The index of spontaneous proliferation correlates with antigen-specific PBMC proliferation to the vaccine antigen KLH. Furthermore, both spontaneous- and antigen-specific proliferation in PBMC cultures are dependent on blood myeloid DCs.

Original languageEnglish (US)
Pages (from-to)288-295
Number of pages8
JournalJournal of Clinical Immunology
Volume25
Issue number3
DOIs
StatePublished - May 1 2005

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Keywords

  • Cytokines
  • T cell immunity
  • Tumor immunity
  • Vaccination

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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