Human invariant Vα24+ natural killer T cells activated by a-galactosylceramide (KRN7000) have cytotoxic anti-tumour activity through mechanisms distinct from T cells and natural killer cells

A. Nicol, M. Nieda, Y. Koezuka, Steven A. Porcelli, K. Suzuki, K. Tadokoro, S. Durrant, T. Juji

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Abstract

Human Vα24 + NKT cells, a subpopulation of natural killer cell receptor (NKR-P1A) expressing T cells with an invariant T-cell receptor (TCR; Vα24JαQ) are stimulated by the glycolipid, α-galactosylceramide (KRN7000), in a CD1d-dependent, TCR-mediated fashion. Little is known about Vα14 + NKT-cell function. The murine counterpart, Vα14 + NKT cells, appear to have an important role in controlling malignancy. There are no human data examining the role of Vα24 + NKT cells in controlling human malignancy. We report that Vα24 + NKT cells have perforin-mediated cytotoxicity against haemopoietic malignancies. Vα24 TCR, CD1d and α-galactosylceramide may all play a role in cytotoxicity but are not absolute requirements. The greatest cytotoxicity was observed against the U937 tumour cell line (95 ± 5% lysis). THP-1, Molt4, CIR cells and allogeneic mismatched dendritic cells were also sensitive to Vα24 + NKT cytotoxicity but neither the NK target, K562, nor lymphokine-activated killer-sensitive Daudi cells, were sensitive. These results indicate a killing pattern distinct from conventional major histocompatibility complex-restricted T cells, NK cells and other cytotoxic lymphoid cells previously described. We conclude that human Vα24 + NKT cells have cytotoxic anti-tumour activity against haemopoietic malignancies through effector mechanisms distinct from conventional T cells and NK cells and that their specific stimulator KRN7000 may have therapeutic potential.

Original languageEnglish (US)
Pages (from-to)229-234
Number of pages6
JournalImmunology
Volume99
Issue number2
DOIs
StatePublished - 2000
Externally publishedYes

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Galactosylceramides
Natural Killer T-Cells
Natural Killer Cells
T-Lymphocytes
Neoplasms
Natural Killer Cell Receptors
Perforin
U937 Cells
Lymphokines
Glycolipids
T-Cell Antigen Receptor
Tumor Cell Line
Major Histocompatibility Complex
Dendritic Cells
KRN 7000
Lymphocytes

ASJC Scopus subject areas

  • Immunology

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Human invariant Vα24+ natural killer T cells activated by a-galactosylceramide (KRN7000) have cytotoxic anti-tumour activity through mechanisms distinct from T cells and natural killer cells. / Nicol, A.; Nieda, M.; Koezuka, Y.; Porcelli, Steven A.; Suzuki, K.; Tadokoro, K.; Durrant, S.; Juji, T.

In: Immunology, Vol. 99, No. 2, 2000, p. 229-234.

Research output: Contribution to journalArticle

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abstract = "Human Vα24 + NKT cells, a subpopulation of natural killer cell receptor (NKR-P1A) expressing T cells with an invariant T-cell receptor (TCR; Vα24JαQ) are stimulated by the glycolipid, α-galactosylceramide (KRN7000), in a CD1d-dependent, TCR-mediated fashion. Little is known about Vα14 + NKT-cell function. The murine counterpart, Vα14 + NKT cells, appear to have an important role in controlling malignancy. There are no human data examining the role of Vα24 + NKT cells in controlling human malignancy. We report that Vα24 + NKT cells have perforin-mediated cytotoxicity against haemopoietic malignancies. Vα24 TCR, CD1d and α-galactosylceramide may all play a role in cytotoxicity but are not absolute requirements. The greatest cytotoxicity was observed against the U937 tumour cell line (95 ± 5{\%} lysis). THP-1, Molt4, CIR cells and allogeneic mismatched dendritic cells were also sensitive to Vα24 + NKT cytotoxicity but neither the NK target, K562, nor lymphokine-activated killer-sensitive Daudi cells, were sensitive. These results indicate a killing pattern distinct from conventional major histocompatibility complex-restricted T cells, NK cells and other cytotoxic lymphoid cells previously described. We conclude that human Vα24 + NKT cells have cytotoxic anti-tumour activity against haemopoietic malignancies through effector mechanisms distinct from conventional T cells and NK cells and that their specific stimulator KRN7000 may have therapeutic potential.",
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AU - Nicol, A.

AU - Nieda, M.

AU - Koezuka, Y.

AU - Porcelli, Steven A.

AU - Suzuki, K.

AU - Tadokoro, K.

AU - Durrant, S.

AU - Juji, T.

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