Abstract:
: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 (T(EM)) 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 T(EM) cells. This programmed response was associated with an interval of antigen-independent interferon-gamma (IFN-gamma) release that facilitated the dynamic expression of the major histocompatibility complex class I restriction element H-2D(b) on 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-gamma entirely abrogated the benefit of the programmed response, whereas transfer of cells unable to respond to IFN-gamma 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.
journal_name
Bloodjournal_title
Bloodauthors
Klebanoff CA,Yu Z,Hwang LN,Palmer DC,Gattinoni L,Restifo NPdoi
10.1182/blood-2008-12-192419subject
Has Abstractpub_date
2009-08-27 00:00:00pages
1776-83issue
9eissn
0006-4971issn
1528-0020pii
blood-2008-12-192419journal_volume
114pub_type
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