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

Here we show that the cell-cycle regulator p21 is involved in immune system function. T lymphocytes from p21(-/-) mice exhibit significant proliferati ve advantage over wild-type cells following prolonged stimulation, but not after primary activation. Consistent with this, p27-deficient mice accumula te abnormal amounts of CD4(+) memory cells, and develop loss of tolerance t owards 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 f or p21 in the control of T-cell proliferation, tolerance to nuclear antigen s, and female-prone lupus. These findings could be the basis for new therap eutic approaches to lupus.