Balance between NF-κB p100 and p52 regulates T cell costimulation dependence.

ABSTRACT: c-IAP1 and c-IAP2 are ubiquitin protein ligases (E3s) that repress noncanonical NF-κB activation. We have created mice that bear a mutation in c-IAP2 that inactivates its E3 activity and interferes, in a dominant-negative fashion, with c-IAP1 E3 activity (c-IAP2(H570A)). The immune response of these animals was explored by infecting them with the Th1-inducing parasite Toxoplasma gondii. Surprisingly, c-IAP2(H570A) mice succumbed because of T cell production of high levels of proinflammatory cytokines. Unlike naive wild-type (WT) cells, which require signals generated by the TCR and costimulatory receptors to become fully activated, naive c-IAP2(H570A) T cells proliferated and produced high levels of IL-2 and IFN-γ to stimulation via TCR alone. c-IAP2(H570A) T cells had constitutive noncano

SUBMITTER: Giardino Torchia ML 

PROVIDER: S-EPMC3538904 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature