CD4+ CD25+ regulatory T cells control the induction of antigen-specific CD4+ helper T cell responses in cancer patients

Blood. 2005 Aug 1;106(3):1008-11. doi: 10.1182/blood-2005-02-0607. Epub 2005 Apr 19.

Abstract

A proportion of cancer patients naturally develop CD4+ T-helper type 1 (Th1) cell responses to NY-ESO-1 that correlate with anti-NY-ESO-1 serum antibodies. To address the role of T-cell regulation in the control of spontaneous tumor immunity, we analyzed NY-ESO-1-specific Th1 cell induction before or after depletion of CD4+CD25+ T cells in vitro. While Th1 cells were generated in the presence of CD25+ T cells in cancer patients seropositive for NY-ESO-1, seronegative cancer patients and healthy donors required CD25+ T-cell depletion for in vitro induction of NY-ESO-1-specific Th1 cells. In vitro, newly generated NY-ESO-1-specific Th1 cells were derived from naive precursors, whereas preexisting memory populations were detectable exclusively in patients with NY-ESO-1 antibody. Memory populations were less sensitive than naive populations to CD4+CD25+ regulatory T cells. We propose that CD4+CD25+ regulatory T cells are involved in the generation and regulation of NY-ESO-1-specific antitumor immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neoplasm / blood
  • Antigens, Neoplasm / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • Case-Control Studies
  • Cell Proliferation
  • Humans
  • Immunologic Memory
  • Interferon-gamma / metabolism
  • Membrane Proteins / immunology
  • Neoplasms / immunology*
  • Receptors, Interleukin-2
  • T-Cell Antigen Receptor Specificity / immunology*
  • Th1 Cells / immunology*

Substances

  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • CTAG1B protein, human
  • Membrane Proteins
  • Receptors, Interleukin-2
  • Interferon-gamma