Abstract
CD1d-restricted natural killer T (NKT) cells play important regulatory roles in various immune responses. NKT cell-derived T helper (Th) 1 cytokines are important in the induction of antitumor immune responses in mice. Because the CD1d-restricted Valpha24(+) Vbeta11(+) NKT cell population in cancer patients is decreased both in size and in its capacity to secrete IFN-gamma, therapeutic strategies based on reconstitution of type 1 polarized Valpha24(+) Vbeta11(+) NKT cells merit additional investigation. Here, we report the simultaneous strong expansion and type 1 polarization of human invariant Valpha24(+) Vbeta11(+) NKT cells using alpha-galactosylceramide-loaded type 1 dendritic cells and interleukin 15. Type 1 polarized Valpha24(+) Vbeta11(+) NKT cells produced high levels of IFN-gamma, tumor necrosis factor alpha, and granulocyte macrophage colony-stimulating factor, and induced strong cytotoxicity in Jurkat cells in an alpha-galactosylceramide-dependent manner. Importantly, the cytokine profile of Valpha24(+) Vbeta11(+) NKT cells that were initially expanded under Th2 polarizing conditions could be reversed to a Th1 cytokine profile, indicating the plasticity of the cytokine profile of the human adult Valpha24(+) Vbeta11(+) NKT cell population.
Original language | English |
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Pages (from-to) | 4101-6 |
Number of pages | 6 |
Journal | Cancer research |
Volume | 63 |
Issue number | 14 |
Publication status | Published - 15 Jul 2003 |
Keywords
- Adult
- Aged
- Antigens, CD/immunology
- Cell Polarity/immunology
- Cytotoxicity, Immunologic
- Dendritic Cells/immunology
- Female
- Galactosylceramides/immunology
- Humans
- Immunotherapy, Adoptive/methods
- Interleukin-12/biosynthesis
- Interleukin-15/biosynthesis
- Jurkat Cells
- Killer Cells, Natural/cytology
- Male
- Middle Aged
- Neoplasms/immunology
- Th2 Cells/immunology