Analysis of human Vα24+ CD4+ NKT cells activated by α- glycosylceramide-pulsed monocyte-derived dendritic cells

Tsuyoshi Takahashi, Mie Nieda, Yasuhiko Koezuka, Andrew Nicol, Steven A. Porcelli, Yoshihide Ishikawa, Kenji Tadokoro, Hisamaru Hirai, Takeo Juji

Research output: Contribution to journalArticle

135 Scopus citations

Abstract

Human Vα24+ NKT cells with an invariant TCR (Vα24-JαQ) have been shown to be specifically activated by synthetic glycolipids such as α- galactosylceramide and α-glucosylceramide in a CD1d-restricted and Vα24 TCR-mediated manner. We recently characterized Vα24+ CD4- CDS- double negative (DN) NKT cells using α-galactosylceramide-pulsed monocyte-derived dendritic cells. Here, we compare Vα24+ CD4+ NKT cells with human Vα24+ DN NKT cells from the same donor using α-galactosylceramide-pulsed monocyte- derived dendritic cells. Human Vα24+ CD4+ NKT cells were phenotypically and functionally similar to the human Vα24+ DN NKT cells characterized previously. Both of them use Vα24-J∅q-Vβ11 TCR and express CD161 (NKRP1A), but not the other NK receptors tested so far. They also produce cytokines such as IL-4 and IFN-γ, and, in regard to IL-4 production, Vα24+ CD4+ NKT cells produce more IL-4 than Vα24+ DN NKT cells. The cells exhibit marked cytotoxic activity against the U937 tumor cell line, but not against the NK target cell line, K562. Although at least some of the factors responsible for the stimulation of Vα24+ NKT cells have been clarified, little is known regarding the killing phase of these cells. Here we show that the cytotoxic activity of Vα24+ NKT cells against U937 cells is mediated mainly through the perforin pathway and that ICAM-1/LFA-1 as well as CD44/hyaluronic acid interactions are important for the effector phase of Vα24+ NKT cell- mediated cytotoxicity against U937 cells.

Original languageEnglish (US)
Pages (from-to)4458-4464
Number of pages7
JournalJournal of Immunology
Volume164
Issue number9
StatePublished - May 1 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Takahashi, T., Nieda, M., Koezuka, Y., Nicol, A., Porcelli, S. A., Ishikawa, Y., Tadokoro, K., Hirai, H., & Juji, T. (2000). Analysis of human Vα24+ CD4+ NKT cells activated by α- glycosylceramide-pulsed monocyte-derived dendritic cells. Journal of Immunology, 164(9), 4458-4464.