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J Immunol. 2004 Jan 1;172(1):104-13.

Activation of resting human primary T cells with chimeric receptors: costimulation from CD28, inducible costimulator, CD134, and CD137 in series with signals from the TCR zeta chain.

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  • 1Celltech R&D, 208 Bath Road, Slough, Berkshire SL1 3WE, United Kingdom. hfinney@celltech.co.uk

Abstract

Chimeric receptors that include CD28 signaling in series with TCRzeta in the same receptor have been demonstrated to activate prestimulated human primary T cells more efficiently than a receptor providing TCRzeta signaling alone. We examined whether this type of receptor can also activate resting human primary T cells, and whether molecules other than CD28 could be included in a single chimeric receptor in series with TCRzeta to mediate the activation of resting human primary T cells. Human CD33-specific chimeric receptors were generated with CD28, inducible costimulator, CD134, or CD137 signaling regions in series with TCRzeta signaling region and transfected by electroporation into resting human primary T cells. Their ability to mediate Ag-specific activation was analyzed in comparison with a receptor providing TCRzeta signaling alone. Inclusion of any of the costimulatory signaling regions in series with TCRzeta enhanced the level of specific Ag-induced IL-2, IFN-gamma, TNF-alpha, and GM-CSF cytokine production and enabled resting primary T cells to survive and proliferate in response to Ag in the absence of any exogenous factors. Inclusion of CD28, inducible costimulator, or CD134 enhanced TCRzeta-mediated, Ag-specific target cell lysis. Chimeric receptors providing B7 and TNFR family costimulatory signals in series with TCRzeta in the same receptor can confer self-sufficient clonal expansion and enhanced effector function to resting human T cells. This type of chimeric receptor may now be used to discover the most potent combination of costimulatory signals that will improve current immunotherapeutic strategies.

PMID:
14688315
[PubMed - indexed for MEDLINE]
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