Cytokine-stimulated T lymphocyte proliferation is regulated by p27(Kip1 1)

S. Zhang, V. A. Lawless, M. H. Kaplan

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

T lymphocyte growth is regulated by the cyclin-dependent kinase inhibitor p27(Kip1). Mice deficient in p27(Kip1) have increased proliferative responses to multiple cytokines, including IL-2, IL-4, and IL-12, but not to anti-CD3. In the absence of p27(Kip1), T cells proliferate faster than control cells, as evidenced by increased [3H]thymidine uptake, increased cell growth and division, and an increased number of cells in S phase. Importantly, this regulation is specific for p27(Kip1) in T cells, because hyperproliferation of T cells from mice deficient in p21(Cip1/Waf1) was not observed. In vivo, there is an expansion of activated/memory CD4+ cells in p27(Kip1)-deficient mice before and after immunization. Furthermore, Ag-stimulated spleen cells from immunized p27(Kip1)-deficient mice demonstrated increased proliferative responses to IL-2 and increased secretion of IFN-γ. Although IL-4 stimulated proliferative responses are diminished in Stat6-deficient T cells, activated T cells from mice doubly deficient in both p27(Kip1) and Stat6 recover normal proliferative responses to IL-4. Together, these data firmly support a role for p27(Kip1) as a negative regulator of cytokine-stimulated T cell growth.

Original languageEnglish (US)
Pages (from-to)6270-6277
Number of pages8
JournalJournal of Immunology
Volume165
Issue number11
DOIs
StatePublished - Dec 1 2000

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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