Costimulation reverses the defect in IL-2 but not effector cytokine production by T cells with impaired IkappaBalpha degradation
| Autor: | T M, Aune, A L, Mora, S, Kim, M, Boothby, A H, Lichtman |
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| Rok vydání: | 1999 |
| Předmět: |
CD4-Positive T-Lymphocytes
Receptor Aggregation NF-kappa B Receptors Antigen T-Cell Mice Transgenic Response Elements Mice Mutant Strains Proto-Oncogene Proteins c-rel DNA-Binding Proteins Interferon-gamma Mice CD28 Antigens NF-KappaB Inhibitor alpha Proto-Oncogene Proteins Mutation Animals Cytokines Interleukin-2 I-kappa B Proteins Interleukin-4 Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 162(10) |
| ISSN: | 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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