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

J. S. Burr, N. D.L. Savage, G. E. Messah, S. L. Kimzey, A. S. Shaw, R. H. Arch, J. M. Green

Research output: Contribution to journalArticlepeer-review

130 Scopus citations


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-XL. Mutation of C-terminal proline residues abrogated the proliferative and cytokine regulatory features of CD28 costimulation while preserving Bcl-XL induction. Conversely, mutation of residues important in phosphatidylinositol 3-kinase activation partially inhibited proliferation but prevented induction of Bcl-XL. Thus the ability of CD28 to regulate proliferation and induction of Bcl-XL map to distinct motifs, suggesting independent signaling cascades modulate these biologic effects.

Original languageEnglish
Pages (from-to)5331-5335
Number of pages5
JournalJournal of Immunology
Issue number9
StatePublished - May 1 2001


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