The cell cycle inhibitor p21 controls T-cell proliferation and sex-linked lupus development

Nat Med. 2000 Feb;6(2):171-6. doi: 10.1038/72272.


Here we show that the cell-cycle regulator p21 is involved in immune system function. T lymphocytes from p21-/- mice exhibit significant proliferative advantage over wild-type cells following prolonged stimulation, but not after primary activation. Consistent with this, p21-deficient mice accumulate abnormal amounts of CD4+ memory cells, and develop loss of tolerance towards nuclear antigens. Similar to human lupus, female p21-deficient mice develop antibodies against dsDNA, lymphadenopathy, and glomerulonephritis, leading to decreased viability. These data demonstrate a specialized role for p21 in the control of T-cell proliferation, tolerance to nuclear antigens, and female-prone lupus. These findings could be the basis for new therapeutic approaches to lupus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Antinuclear / immunology
  • Cell Division / physiology*
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / physiology*
  • DNA / immunology
  • Female
  • Genetic Linkage*
  • Glomerulonephritis / immunology
  • Immunologic Memory
  • Lupus Vulgaris / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Sex Factors
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology


  • Antibodies, Antinuclear
  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA