Immunoregulatory effects of CD4+ T helper subsets in human melanoma

Surgery. 1995 Apr;117(4):365-72. doi: 10.1016/s0039-6060(05)80054-6.


Background: The elucidation of CD4+ T helper (Th) cell traits is important for the understanding of immunoregulatory mechanisms in patients with cancer, in particular the Th-cell effect on cytotoxic CD8+ tumor-specific lymphocytes (CTL).

Methods: Sixty-six T-cell receptor alpha beta+/CD4+ clones were generated from tumor-infiltrating lymphocytes of five patients with melanoma and classified into subsets by cytokine production. Transwell experiments were performed to test how the soluble factors of each Th-clone subset affected the cytotoxicity of the tumor-specific CTL against autologous tumor.

Results: Th0 clones enhanced cytotoxicity of the CD8+ CTL compared with control CTL cultured in cytokine-free medium. Th1-clone supernatant also enhanced cytotoxicity by CD8+ CTL. In contrast, Th2 clones decreased killing compared with control CTL. Replacement of the Th clones by exogenous interleukin (IL)-2 in concentrations similar to that produced by Th0 and Th1 clones enhanced cytotoxicity. However, suppression of cytotoxicity was observed when similar concentrations of IL-4 were added instead. The helper effect of Th0-soluble factors could be inhibited by anti-IL-2 antibody, whereas anti-IL-4 antibody did not show a significant enhancement.

Conclusions: The majority of the CD4+ tumor-infiltrating lymphocytes (Th0) in patients with melanoma enhance the CTL response to autologous tumor by their soluble factors, whereas Th2 cells suppress the CTL response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / analysis
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Clone Cells
  • Culture Techniques / methods
  • Cytokines / biosynthesis
  • Cytotoxicity, Immunologic
  • HLA-DR Antigens / analysis
  • Humans
  • Immunophenotyping
  • Interferon-gamma / biosynthesis
  • Interleukins / biosynthesis
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Melanoma / immunology*
  • Melanoma / pathology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*


  • Antigens, CD
  • Cytokines
  • HLA-DR Antigens
  • Interleukins
  • Interferon-gamma