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

S. Zhang, V. A. Lawless, Mark Kaplan

Research output: Contribution to journalArticle

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

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Cytokines
T-Lymphocytes
Interleukin-4
Interleukin-2
Growth
Cyclin-Dependent Kinase Inhibitor p27
Interleukin-12
S Phase
Cell Division
Thymidine
Immunization
Spleen
Cell Count

ASJC Scopus subject areas

  • Immunology

Cite this

Cytokine-stimulated T lymphocyte proliferation is regulated by p27(Kip1 1). / Zhang, S.; Lawless, V. A.; Kaplan, Mark.

In: Journal of Immunology, Vol. 165, No. 11, 01.12.2000, p. 6270-6277.

Research output: Contribution to journalArticle

Zhang, S. ; Lawless, V. A. ; Kaplan, Mark. / Cytokine-stimulated T lymphocyte proliferation is regulated by p27(Kip1 1). In: Journal of Immunology. 2000 ; Vol. 165, No. 11. pp. 6270-6277.
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