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J Immunol. 2001 May 1;166(9):5331-5.

Cutting edge: distinct motifs within CD28 regulate T cell proliferation and induction of Bcl-XL.

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  • 1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.


CD28 provides an important costimulatory signal in T cell activation that regulates multiple cellular processes including proliferation and survival. Several signal transduction pathways are activated by CD28; however, the precise biochemical mechanism by which CD28 regulates T cell function remains controversial. Retroviral gene transfer into primary T cells from TCR-transgenic, CD28-deficient mice was used to determine the specific sequences within CD28 that determine function. Discrete regions of the cytoplasmic domain of CD28 were identified that differentially regulate T cell proliferation and induction of the anti-apoptotic protein Bcl-X(L). Mutation of C-terminal proline residues abrogated the proliferative and cytokine regulatory features of CD28 costimulation while preserving Bcl-X(L) induction. Conversely, mutation of residues important in phosphatidylinositol 3-kinase activation partially inhibited proliferation but prevented induction of Bcl-X(L.) Thus the ability of CD28 to regulate proliferation and induction of Bcl-X(L) map to distinct motifs, suggesting independent signaling cascades modulate these biologic effects.

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