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24+ CD4+ NKT Cells Activated by -Glycosylceramide-Pulsed Monocyte-Derived Dendritic Cells
*
Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan;
Department of Research, Japanese Red Central Blood Center, Tokyo, Japan;
Pharmaceutical Research Laboratory, Gunma, Japan;
§
Queensland Institute of Medical Research, Royal Brisbane Hospital, Brisbane, Australia; and
¶
Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital, Boston, MA 02115
Human V
24+ NKT cells with an invariant TCR
(V24-JQ) have been shown to be specifically activated by
synthetic glycolipids such as -galactosylceramide and
-glucosylceramide in a CD1d-restricted and V24 TCR-mediated
manner. We recently characterized V24+ CD4-
CD8- double negative (DN) NKT cells using
-galactosylceramide-pulsed monocyte-derived dendritic cells. Here,
we compare V24+ CD4+ NKT cells with human
V24+ DN NKT cells from the same donor using
-galactosylceramide-pulsed monocyte-derived dendritic cells. Human
V24+ CD4+ NKT cells were phenotypically and
functionally similar to the human V24+ DN NKT cells
characterized previously. Both of them use V24-JQ-Vß11 TCR and
express CD161 (NKR-P1A), but not the other NK receptors tested so far.
They also produce cytokines such as IL-4 and IFN-
, and, in regard to
IL-4 production, V24+ CD4+ NKT cells produce
more IL-4 than V24+ 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 V24+ NKT
cells have been clarified, little is known regarding the killing phase
of these cells. Here we show that the cytotoxic activity of
V24+ 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 V24+ NKT cell-mediated cytotoxicity against U937
cells.
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