| First Author | Aune TM | Year | 1999 |
| Journal | J Immunol | Volume | 162 |
| Issue | 10 | Pages | 5805-12 |
| PubMed ID | 10229814 | Mgi Jnum | J:119787 |
| Mgi Id | MGI:3703269 | Doi | 10.4049/jimmunol.162.10.5805 |
| Citation | Aune TM, et al. (1999) Costimulation reverses the defect in IL-2 but not effector cytokine production by T cells with impaired IkappaBalpha degradation. J Immunol 162(10):5805-12 |
| abstractText | Although the transcriptional basis for states of unresponsiveness in primary T cells is unclear, tolerant B lymphocytes exhibit inhibition of both c-Jun N-terminal kinase induction and IkappaBalpha (inhibitor of NF-kappaBalpha) degradation, leading to lower levels of both nuclear AP-1 and NF-kappaB. Expression of an IkappaBalpha mutant resistant to signal-induced degradation in transgenic T cells caused markedly deficient effector cytokine (IL-4, IFN-gamma) production after primary TCR stimulation despite a detectable level of nuclear NF-kappaB. A TCR response element from the IFN-gamma promoter, despite lacking detectable NF-kappaB/Rel sites, was also unresponsive to TCR ligation. Nuclear induction of AP-1 proteins in response to T cell activation was diminished in transgenic T cells. Costimulation induced by anti-CD28 mAb increased IL-2 production, but failed to reverse the defects in effector cytokine production. Taken together, these data indicate that impaired NF-kappaB/Rel signaling in T cells interferes with the signal transduction pathways required for efficient induction of effector cytokine production. |
