http://precedings.nature.com/users/db67003769555d515d6946ca29993af1/ Documents posted by Ashwani Khanna Nature Publishing Group en Nature Precedings http://precedings.nature.com/images/header_logo.gif http://precedings.nature.com http://precedings.nature.com/documents/3378/version/1 Background: Uncontrolled proliferation of T-cells is considered a barrier to the induction of transplantation tolerance by T regulatory cells. Therefore, cyclin kinase inhibitor p21, one of the most potent inhibitors of cell proliferation, may exert an important role in the induction/generation of T regulatory cells.Methods: CD4+CD25+ and CD4+CD25- cells were isolated from normal healthy blood donors (n=6), p21-/- mice (n=9) and wild type mice (n=9). Proliferation with and without cyclosporine was quantified by 3H-thymidine uptake assay (expressed as counts per minute) and FoxP3 mRNA was studied by real-time quantitative RT-PCR. Results: The difference in proliferation (p+CD25- T cells, CD4+25+ T cells from p21-/- mice lacked FoxP3 gene expression. T lymphocytes from wild type inhibited the proliferation of T lymphocytes from p21-/- mice similar to the effect of CD4+CD25+ T cells on the proliferation of CD4+CD25- cells. Conclusions: Presence of the p21 creates a milieu favorable for immune tolerance and consistent with antiproliferative and immunosuppressive effect of CD4+CD25+ T-regulatory cells. These findings support the notion that p21 could be used clinically in controlling allo-immune activation to achieve prolongation of graft survival. http://precedings.nature.com/documents/3378/version/1 Mon, 29 Jun 2009 12:17:13 UTC Cyclin kinase inhibitor p21: a mediator of immune tolerance: direct and indirect evidence hdl:10101/npre.2009.3378.1 2009-06-29 Ashwani Khanna Nature Precedings 2009-06-29T12:17:13Z Manuscript Immunology http://creativecommons.org/licenses/by/3.0/