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Cyclin kinase inhibitor p21: a mediator of immune tolerance: direct and indirect evidence

Ashwani Khanna¹

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1. University of Maryland, Baltimore, USA

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Document Type:

Manuscript

Date:

Received 26 June 2009 19:29 UTC; Posted 29 June 2009

Subjects:

Immunology

Tags:

• p21
• tolerance
• transplantation
• FoxP3
• proliferation

Abstract:

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<0.002) lower (2.6 ± 0.8%) than wild type mice (14.5 ± 1.6%,) and similar to CD4⁺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.

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This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Khanna, Ashwani. Cyclin kinase inhibitor p21: a mediator of immune tolerance: direct and indirect evidence. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2009.3378.1> (2009)

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