CD4+ CD25+ regulatory T cells control the induction of antigen-specific CD4+ helper T cell responses in cancer patients.
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.
Nishikawa
Hiroyoshi
H
Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Box 32/Rm K-817, New York, NY 10021, USA.
Jäger
Elke
E
Ritter
Gerd
G
Old
Lloyd J
LJ
Gnjatic
Sacha
S
D000912:Antibodies, Neoplasm / Q000097:blood; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology; D009369:Neoplasms / Q000276:immunology*; D015375:Receptors, Interleukin-2; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D008565:Membrane Proteins; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma