CD4(+), HLA Class I-restricted, Cytolytic T-lymphocyte Clone Against Primary Malignant Melanoma Cells

Int J Cancer. 2000 Jan 15;85(2):253-9. doi: 10.1002/(sici)1097-0215(20000115)85:2<253::aid-ijc17>3.0.co;2-u.

Abstract

The involvement of HLA-class I in target cell lysis by CD4(+) cytolytic T cells (CTL) has been a controversial issue. A CTL clone of CD4 phenotype was derived from the peripheral blood lymphocytes of a patient with primary melanoma. The CTL clone stably lysed the autologous primary melanoma cells for approximately 9 months in culture. Both the Valpha2/Vbeta8 T-cell receptor and CD4 were involved in CTL cytotoxicity. Of a large panel of allogeneic primary and metastatic melanoma or colorectal carcinoma cells, autologous and allogeneic Epstein-Barr virus-transformed B cells and autologous fibroblasts, only allogeneic metastatic melanoma cells matched with the autologous tumor cells for HLA-class I (B57[17]) were lysed and induced IFN-gamma secretion by the CTL clone. Lysis of the autologous tumor cells was significantly blocked by monoclonal antibody to HLA-B17. Importantly, allogeneic, HLA-class I- and class II-unmatched melanoma cells were lysed by the CTL only following transfection of the cells with B57[17] cDNA. Our results provide direct evidence for the involvement of both CD4 and HLA-class I in tumor cell lysis by CD4(+) CTL.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antibodies, Monoclonal / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Division
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic
  • DNA, Complementary / genetics
  • HLA-B Antigens / genetics
  • HLA-B Antigens / immunology
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Male
  • Melanoma / immunology*
  • Receptors, Antigen, T-Cell / immunology
  • Skin Neoplasms / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Cytokines
  • DNA, Complementary
  • HLA-B Antigens
  • HLA-B57 antigen
  • Histocompatibility Antigens Class I
  • Receptors, Antigen, T-Cell