Inefficient ZAP-70 phosphorylation and decreased thymic selection in vivo result from inhibition of NF-kappaB/Rel.

Mora AL, Stanley S, Armistead W, Chan AC, Boothby M
J Immunol. 2001 167 (10): 5628-35

PMID: 11698434 · DOI:10.4049/jimmunol.167.10.5628

Signaling from the TCR regulates T lymphoid survival, deletion by apoptosis, and selective clonal expansion. One set of signaling pathways activated during thymic selection leads to degradation of a cytosolic retention protein, the inhibitor of kappaB (IkappaB)alpha, followed by nuclear translocation of the NF-kappaB/Rel family of transcription factors. It has been found previously that NF-kappaB proteins mediate a pathway signaling the survival of mature T cells and protection of thymocytes against TNF-induced apoptosis. In contrast, we show in this study that a transgenic inhibitor of NF-kappaB/Rel signaling interferes with the negative selection of immature thymocytes by endogenous MHC ligands in vivo. Positive selection of the H-Y TCR also was diminished. This attenuation of thymic selection efficiency was associated with decreased ZAP-70 phosphorylation and TCR signaling of CD69 induction. These findings demonstrate that the NF-kappaB transcriptional pathway plays an important role in normal processes of clonal deletion and they indicate that the NF-kappaB/IkappaB axis can regulate the efficiency of TCR signaling.

MeSH Terms (19)

Animals Cells, Cultured Cell Survival Clonal Deletion DNA-Binding Proteins Female I-kappa B Proteins Mice Mice, Transgenic NF-kappa B NF-KappaB Inhibitor alpha Phosphorylation Protein-Tyrosine Kinases Proto-Oncogene Proteins c-rel Receptors, Antigen, T-Cell Signal Transduction T-Lymphocytes Thymus Gland ZAP-70 Protein-Tyrosine Kinase

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