Therapeutic activation of Vα24+Vβ11+ NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity

M Nieda, M Okai, A Tazbirkova, H Lin, A Yamaura… - Blood, 2004 - ashpublications.org
M Nieda, M Okai, A Tazbirkova, H Lin, A Yamaura, K Ide, R Abraham, T Juji, DJ Macfarlane…
Blood, 2004ashpublications.org
Human Vα24+ Vβ11+ natural killer T (NKT) cells are a distinct CD1d-restricted lymphoid
subset specifically and potently activated by α-galactosylceramide (α-GalCer)(KRN7000)
presented by CD1d on antigen-presenting cells. Preclinical models show that activation of
Vα24+ Vβ11+ NKT cells induces effective antitumor immune responses and potentially
important secondary immune effects, including activation of conventional T cells and NK
cells. We describe the first clinical trial of cancer immune therapy with α-GalCer–pulsed …
Abstract
Human Vα24+Vβ11+ natural killer T (NKT) cells are a distinct CD1d-restricted lymphoid subset specifically and potently activated by α-galactosylceramide (α-GalCer) (KRN7000) presented by CD1d on antigen-presenting cells. Preclinical models show that activation of Vα24+Vβ11+ NKT cells induces effective antitumor immune responses and potentially important secondary immune effects, including activation of conventional T cells and NK cells. We describe the first clinical trial of cancer immune therapy with α-GalCer–pulsed CD1d-expressing dendritic cells. The results show that this therapy has substantial, rapid, and highly reproducible specific effects on Vα24+Vβ11+ NKT cells and provide the first human in vivo evidence that Vα24+Vβ11+ NKT cell stimulation leads to activation of both innate and acquired immunity, resulting in modulation of NK, T-, and B-cell numbers and increased serum interferon-γ. We present the first clinical evidence that Vα24+Vβ11+ NKT cell memory produces faster, more vigorous secondary immune responses by innate and acquired immunity upon restimulation.
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