Autonomous induction of proliferation, JNK and NF- Kappa B activation in primary resting T cells by mobilized CD28

Induction of proliferation in primary resting T cells requires engagement of both the antigen-specific TCR and the co-stimulatory receptor CD28. Here we report that CD28 functions as an autonomous mitogenic receptor which is mobilized by TCR signaling through cytoskeletal rearrangement. Shortcutting...

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Bibliographic Details
Published in:European journal of immunology 2000-03, Vol.30 (3), p.876-882
Main Authors: Bischof, A, Hara, T, Lin, Chia-Huey, Beyers, AD, Huenig, T
Format: Article
Language:English
Subjects:
CD28 antigen
JNK protein
NF-^KB protein
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Summary:Induction of proliferation in primary resting T cells requires engagement of both the antigen-specific TCR and the co-stimulatory receptor CD28. Here we report that CD28 functions as an autonomous mitogenic receptor which is mobilized by TCR signaling through cytoskeletal rearrangement. Shortcutting of TCR-dependent CD28 recruitment by stimulation with monoclonal antibodies specific for mobilized CD28 results in maximum proliferation and IL-2 secretion in primary resting T cells without activation of ZAP-70, a central component of the TCR's signal transduction machinery. Engagement of mobilized CD28 fully activates the c-Jun N-terminal kinase cascade and translocation of NF- Kappa B, two key targets of signal integration in co-stimulation. We propose a two-step activation model for co-stimulation in primary resting T cells in which antigen recognition recruits co-stimulatory receptors which then autonomously transduce signals promoting T cell proliferation.
ISSN:0014-2980
DOI:10.1002/1521-4141(200003)30:3<876::AID-IMMU876>3.3.CO;2-D