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Sustained B7/CD28 interactions and resultant phosphatidylinositol 3‐kinase activity maintain G 1 →S phase transitions at an optimal rate
Author(s) -
Bonnevier Jody L.,
Yarke Cory A.,
Mueller Daniel L.
Publication year - 2006
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200535626
Subject(s) - cd28 , phosphatidylinositol , biology , t cell receptor , t cell , microbiology and biotechnology , protein kinase b , pi3k/akt/mtor pathway , cell division , signal transduction , cell , immunology , immune system , biochemistry
Abstract 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by the TCR and CD28 maintained the blasting cell division rate at a maximal level beyond 24 h even when IL‐2 was withdrawn, neutralized, or exhausted.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.