The p110δ Isoform of Phosphoinositide 3-Kinase Controls Clonal Expansion and Differentiation of Th Cells

摘要: The role of PI3K in T cell activation and costimulation has been controversial. We previously reported that a kinase-inactivating mutation (D910A) the p110delta isoform results normal development, but impaired TCR-stimulated proliferation vitro. This proliferative defect can be overcome by providing CD28 costimulation, which raises question as to whether activity plays vivo, occurs primarily context costimulation. In this study, we show signaling pathway CD28-costimulated D910A/D910A cells is impaired, ERK phosphorylation NF-kappaB nuclear translocation are unaffected. Under vitro conditions physiological Ag presentation showed survival, underwent fewer divisions. Differentiation along Th1 Th2 lineages was could not rescued exogenous cytokines Adoptive transfer immunization experiments mice revealed clonal expansion differentiation response were also compromised. Thus, contributes significantly Th