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

Nature Medicine volume 6, pages 171–176 (2000)Cite this article

Abstract

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.

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Figure 1: Proliferative responses of p21−/− CD4+ T cells.
Figure 2: Lymphadenopathy, splenomegaly, and memory lymphocyte accumulation in p21−/− mice.
Figure 3: Glomerulonephritis development in p21−/− mice.
Figure 4: Total IgG and autoantibody profiles.

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Acknowledgements

We thank M. Cohn and A.N. Theofilopoulos for discussion and comments. We are also grateful to G. Hannon for the gift of p21−/− mice, A. Rebollo for IL-4, M.C. Moreno-Ortiz for assistance with FACS analysis C. Alonso for help with statistical analyses following FACS analysis and C. Mark for editorial assistance. The Department of Immunology and Oncology was founded and is supported by the Spanish Research Council (CSIC) and Pharmacia & Upjohn.

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Authors and Affiliations

  1. Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Cantoblanco, Madrid, E-28049, Spain

    Dimitrios Balomenos, Juan Martín-Caballero, Maria I. García, Ignacio Prieto, Manuel Serrano & Carlos Martínez-A

  2. Departamento de Patología Animal II, Facultad de Veterinaria, Universidad Complutense de Madrid, Spain

    Juana M. Flores

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  1. Dimitrios Balomenos
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Correspondence to Dimitrios Balomenos.

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Balomenos, D., Martín-Caballero, J., García, M. et al. The cell cycle inhibitor p21 controls T-cell proliferation and sex-linked lupus development. Nat Med 6, 171–176 (2000). https://doi.org/10.1038/72272

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