NF-κB in Th2 cells : delayed and long-lasting induction through the TCR complex

Abstract

Nucelar NF O B was analyzed in murine Th2 cells after stimulation via the TCR pathway. Signals delivered through the TCR/CD3 complex induced active NF O B translocation to the nucleus of Th2 cells after a late phase (24 h) of the activation process, which is in contrast to the rapid appearance of nuclear NF O B (3 h) in Th1 cells after the same stimulation. The slow kinetic of NF O B nuclear uptake in Th2 cells was not accelerated by CD28 triggering or under stimulation with antigen plus antigen-presenting cells. Th1 and Th2 cells were also different in the composition of NF O B complexes induced. Whereas in Th1 cells TCR triggering induced the presence of nuclear p50.p65 heterodimers, in Th2 cells the complexes induced were shown to be composed of p65 plus another NF O B protein distinct from p50. The delayed NF O B induction in Th2 cells was dependent on protein synthesis and the significance of this is discussed.

A sustained activation of PI3K/NF-κB pathway is critical for the survival of chronic lymphocytic leukemia B cells

“…Furthermore and in agreement with other studies, 38 stimulation of B-CLL cells with anti-CD40 induced high levels of NF-kB activity. To confirm the specificity of the NF-kB signal, a cold oligonucleotide competition assay with 50-fold molar excess of an unlabeled and unrelated competitor 39 was used (Figure 6b). Supershift assay showed that NF-kB complexes translocated predominantly p50-p65 heterodimers to the nuclear extracts (Figure 6c), as previously reported in normal and B-CLL cells.…”

“…39 Nuclear proteins (2 mg) were incubated for 10 min in a final volume of 10 ml with 200 ng poly(dIdC) (Amersham Biosciences) before addition of 0.4 ng of 5 0 -end labelled ds-oligonucleotide kB, which contains an NF-kB binding site (5 0 CAA CGG CAG GGG AAT CTC CCT CTC CTT 3 0 ). 40 Binding reactions were allowed during 30 min at room temperature and electrophoresed in a 5% polyacrylamide gel in TBE (0.5 Â ).…”

IL-18 Enhances IL-4 Production by Ligand-Activated NKT Lymphocytes: A Pro-Th2 Effect of IL-18 Exerted Through NKT Cells

“…Taken together, these results suggest that IL-18 exerts its action on IL-4 production by NKT lymphocytes by amplifying the signaling pathway initiated by TCR/CD3 cross-linking. This might eventually occur through activation of NF-B, a NF that has been implicated in the transcription of IL-4 (36) and whose activation in response to IL-18 and TCR cross-linking has been reported (23,37). Alternatively, increased IL-4 production might also be promoted by the nuclear AP-1, whose activation by IL-18 has been suggested (38) and whose binding to the IL-4 promoter, possibly in combination with other NFs, triggers IL-4 transcription (39).…”

Nuclear Factor-κB Dimer Exchange Promotes a p21waf1/cip1 Superinduction Response in Human T Leukemic Cells

“…Studies have shown that T-cell receptor engagement of Th1 T-helper cells leads to rapid activation of a p50:p65 heterodimer, whereas similar stimulation of Th2 cells leads to delayed activation of p65 complexes devoid of the p50 subunit, thereby possibly contributing to differential cytokine gene regulation (31). A more recent study has shown that differential induction of cRel-containing NF-nB complexes regulates cytokine-mediated priming of naive T cells to overcome their intrinsic refractoriness for cytokine production in response to T-cell receptor engagement (32).…”