Immunoregulatory effects of CD4 + T helper subsets in human melanoma

• Published in: Surgery 1995-04, Vol.117 (4), p.365-372
• Main Authors: Lee, Kyung-Yung, Goedegebuure, Peter S., Linehan, David C., Eberlein, Timothy J.
• Format: Article
• Language: English
• Subjects: Antigens, CD - analysis; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; Cell Line; Clone Cells; Culture Techniques - methods; Cytokines - biosynthesis; Cytotoxicity, Immunologic; Dermatology; HLA-DR Antigens - analysis; Humans; Immunophenotyping; Interferon-gamma - biosynthesis; Interleukins - biosynthesis; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - pathology; Medical sciences; Melanoma - immunology; Melanoma - pathology; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Helper-Inducer - immunology; Tumors of the skin and soft tissue. Premalignant lesions
• ISSN: 0039-6060; 1532-7361
• 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 αβ +/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.