Tumor-Specific Human CD4+ Regulatory T Cells and Their Ligands: Implications for Immunotherapy

Helen Yicheng Wang, Dean A. Lee, Guangyong Peng, Zhong Guo, Yanchun Li, Yukiko Kiniwa, Ethan M. Shevach, Rongfu Wang

Research output: Contribution to journalArticlepeer-review

496 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)107-118
Number of pages12
Issue number1
StatePublished - Jan 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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