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Sustained B7/CD28 Interactions And Resultant Phosphatidylinositol 3‐kinase Activity Maintain G1→S Phase Transitions At An Optimal Rate
J. Bonnevier, Cory A. Yarke, D. Mueller
Published 2006 · Biology, Medicine
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Twenty‐four hours of TCR engagement and CD28 costimulation was found sufficient to elicit an optimal rate of cell division over a 72‐h period only when a high concentration of IL‐2 was produced in the culture and remained readily available to the CD4+ T cells. The cell division response could be aborted following 24 h of stimulation by the simultaneous abrogation of IL‐2R signaling and the blockade of CD28 or TCR ligands. Biochemical and pharmacologic studies indicated that a phosphatidylinositol 3‐kinase‐Akt signaling cascade costimulated by the TCR and CD28 maintained the blasting cell division rate at a maximal level beyond 24 h even when IL‐2 was withdrawn, neutralized, or exhausted. These data show that CD4+ T cells remain sensitive to antigens (Ag) and costimulatory signals throughout the clonal expansion response. Furthermore, only those T cells that perceive the presence of a continued threat in the form of Ag/MHC complexes and B7 costimulatory ligands or a high concentration of a growth factor are directed to remain in cell cycle.
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