| Autor: |
Klebanoff, Christopher A., Yu, Zhiya, Hwang, Leroy N., Palmer, Douglas C., Gattinoni, Luca, Restifo, Nicholas P. |
| Zdroj: |
Blood; August 2009, Vol. 114 Issue: 9 p1776-1783, 8p |
| Abstrakt: |
Naive and memory CD8+T cells can undergo programmed activation and expansion in response to a short T-cell receptor stimulus, but the extent to which in vitro programming can qualitatively substitute for an in vivo antigen stimulation remains unknown. We show that self-/tumor-reactive effector memory CD8+T cells (TEM) programmed in vitro either with peptide-pulsed antigen-presenting cells or plate-bound anti-CD3/anti-CD28 embark on a highly stereotyped response of in vivo clonal expansion and tumor destruction nearly identical to that of vaccine-stimulated TEMcells. This programmed response was associated with an interval of antigen-independent interferon-γ (IFN-γ) release that facilitated the dynamic expression of the major histocompatibility complex class I restriction element H-2Dbon responding tumor cells, leading to recognition and subsequent tumor lysis. Delaying cell transfer for more than 24 hours after stimulation or infusion of cells deficient in IFN-γ entirely abrogated the benefit of the programmed response, whereas transfer of cells unable to respond to IFN-γ had no detriment to antitumor immunity. These findings extend the phenomenon of a programmable effector response to memory CD8+T cells and have major implications for the design of current adoptive-cell transfer trials. |
| Databáze: |
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