CD4+CD25- T cells transduced to express MHC class I-restricted epitope-specific TCR synthesize Th1 cytokines and exhibit MHC class I-restricted cytolytic effector function in a human melanoma model

J Immunol. 2008 Jul 15;181(2):1063-70. doi: 10.4049/jimmunol.181.2.1063.


Cytolytic T cell-centric active specific and adoptive immunotherapeutic approaches might benefit from the simultaneous engagement of CD4(+) T cells. Considering the difficulties in simultaneously engaging CD4(+) and CD8(+) T cells in tumor immunotherapy, especially in an Ag-specific manner, redirecting CD4(+) T cells to MHC class I-restricted epitopes through engineered expression of MHC class I-restricted epitope-specific TCRs in CD4(+) T cells has emerged as a strategic consideration. Such TCR-engineered CD4(+) T cells have been shown to be capable of synthesizing cytokines as well as lysing target cells. We have conducted a critical examination of functional characteristics of CD4(+) T cells engineered to express the alpha- and beta-chains of a high functional avidity TCR specific for the melanoma epitope, MART-1(27-35), as a prototypic human tumor Ag system. We found that unpolarized CD4(+)CD25(-) T cells engineered to express the MART-1(27-35) TCR selectively synthesize Th1 cytokines and exhibit a potent Ag-specific lytic granule exocytosis-mediated cytolytic effector function of comparable efficacy to that of CD8(+) CTL. Such TCR engineered CD4(+) T cells, therefore, might be useful in clinical immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Line, Tumor
  • Cytokines / biosynthesis*
  • Cytokines / immunology
  • Cytotoxicity, Immunologic*
  • Epitopes / immunology*
  • Epitopes / metabolism
  • Genetic Vectors
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Melanoma / immunology*
  • Melanoma / metabolism
  • Neoplasm Proteins / immunology*
  • Neoplasm Proteins / metabolism
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Transduction, Genetic
  • Transgenes


  • Cytokines
  • Epitopes
  • Histocompatibility Antigens Class I
  • MART-1-Melan-A(27-35) epitope
  • Neoplasm Proteins
  • Receptors, Antigen, T-Cell