Down-regulation of p27Kip1 expression is required for development and function of T cells

T. Tsukiyama, N. Ishida, M. Shirane, Y. A. Minamishima, S. Hatakeyama, M. Kitagawa, K. Nakayama, K. I. Nakayama

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Abstract

The proliferation of T cells is regulated in a development-dependent manner, but it has been unclear whether proliferation is essential for T cell differentiation. The cyclin-dependent kinase inhibitor p27Kip1 is abundant throughout development in cells of the T cell lineage, with the exception of late stage CD4-CD8- thymocytes and activated mature T cells, both of which show a high rate of proliferation. The role of down-regulation of p27Kip1 expression in T cell development and function has now been investigated by the generation and characterization of three strains of p27 transgenic mice that express the transgene at various levels specifically in the T cell lineage. The numbers of thymocytes at CD4+CD8+, CD4+CD8-, and CD4-CD8+ stages of development as well as those of mature T cells in peripheral lymphoid tissues were reduced in transgenic mice in a manner dependent on the level of p27Kip1 expression. The development of thymocytes in the transgenic strain in which p27Kip1 is most abundant (p27-Tghigh mice) appeared to be blocked at the CD4-CD8-CD25+CD44low stage. Peripheral T cells from p27-Tghigh mice exhibited a reduced ability to proliferate in response to mitogenic stimulation compared with wild-type T cells. Moreover, Ag-induced formation of germinal centers and Ig production were defective in p27-Tghigh mice. These results suggest that down-regulation of p27Kip1 expression is required for the development, proliferation, and immunoresponsiveness of T cells.

Original languageEnglish
Pages (from-to)304-312
Number of pages9
JournalJournal of Immunology
Volume166
Issue number1
DOIs
Publication statusPublished - 2001 Jan 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Tsukiyama, T., Ishida, N., Shirane, M., Minamishima, Y. A., Hatakeyama, S., Kitagawa, M., Nakayama, K., & Nakayama, K. I. (2001). Down-regulation of p27Kip1 expression is required for development and function of T cells. Journal of Immunology, 166(1), 304-312. https://doi.org/10.4049/jimmunol.166.1.304