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

✍ Scribed by Astrid Bischof; Toyomichi Hara; Chia-Huey Lin; Albertus D. Beyers; Thomas Hünig

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 139 KB
• Volume: 30
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/1521-4141(200003)30:3<876::aid-immu876>3.0.co;2-m

✦ Synopsis

Induction of proliferation in primary resting T cells requires engagement of both the antigenspecific 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-O 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.