Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy.
Regulatory T cells play an important role in the maintenance of immunological self-tolerance by suppressing immune responses against autoimmune diseases and cancer. Little is known, however, about the nature of the physiological target antigens for CD4(+) regulatory T (Treg) cells. Here we report the identification of the LAGE1 protein as a ligand for tumor-specific CD4(+) Treg cell clones generated from the tumor-infiltrating lymphocytes (TILs) of cancer patients. Phenotypic and functional analyses demonstrated that they were antigen-specific CD4(+) Treg cells expressing CD25 and GITR molecules and possessing suppressive activity on the proliferative response of naive CD4(+) T cells to anti-CD3 antibody stimulation. Ligand-specific activation and cell-cell contact were required for TIL102 Treg cells to exert suppressive activity on CD4(+) effector cells. These findings suggest that the presence of tumor-specific CD4(+) Treg cells at tumor sites may have a profound effect on the inhibition of T cell responses against cancer.
Wang
Helen Y
HY
The Center for Cell and Gene Therapy and Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Lee
Dean A
DA
Peng
Guangyong
G
Guo
Zhong
Z
Li
Yanchun
Y
Kiniwa
Yukiko
Y
Shevach
Ethan M
EM
Wang
Rong Fu
RF
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D051858:Forkhead Transcription Factors; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D008024:Ligands; D008565:Membrane Proteins; D009369:Neoplasms / Q000276:immunology*; D010641:Phenotype; D011506:Proteins / Q000235:genetics
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C104948:CTAG1B protein, human; C510162:CTAG2 protein, human; D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D008024:Ligands; D008565:Membrane Proteins; D011506:Proteins; D007371:Interferon-gamma