Journal
NATURE MEDICINE
Volume 6, Issue 2, Pages 171-176Publisher
NATURE AMERICA INC
DOI: 10.1038/72272
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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, p27-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.
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