TY - JOUR
T1 - 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
AU - Nicol, A.
AU - Nieda, M.
AU - Koezuka, Y.
AU - Porcelli, S.
AU - Suzuki, K.
AU - Tadokoro, K.
AU - Durrant, S.
AU - Juji, T.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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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U2 - 10.1046/j.1365-2567.2000.00952.x
DO - 10.1046/j.1365-2567.2000.00952.x
M3 - Article
C2 - 10692041
AN - SCOPUS:0034133499
SN - 0019-2805
VL - 99
SP - 229
EP - 234
JO - Immunology
JF - Immunology
IS - 2
ER -