NDLI: p27Kip1 Negatively Regulates the Magnitude and Persistence of CD4 T Cell Memory

Content Provider	PubMed Central
Author	Jatzek, Anna Tejera, Melba Marie Singh, Anju Sullivan, Jeremy A. Plisch, Erin H. Suresh, M.
Abstract	Much is known about the differentiation of naïve T cells into distinct lineages of effector cells, but the molecular mechanisms underlying the generation and maintenance of CD4 T cell memory are poorly characterized. Our studies ascribe a novel role for the cell cycle regulator p27Kip1, as a prominent negative regulator of the establishment and long-term maintenance of TH1 CD4 T cell memory. We demonstrate that p27Kip1 might restrict the differentiation and survival of memory precursors by increasing the T-bet: Bcl-6 ratio in effector CD4 T cells. Promoting apoptosis and contraction of effector CD4 T cells by mechanisms that are at least in part T cell intrinsic, p27Kip1 markedly limits the abundance of memory CD4 T cells. Furthermore, we causally link p27Kip1-dependent apoptosis to the decay of CD4 T cell memory, possibly by repressing the expression of γ-chain receptors and the downstream effector of the Wnt/β-catenin signaling pathway, Tcf-1. We extend these findings by showing that the antagonistic effects of p27Kip1 on CD4 T cell memory requires its cyclin dependent kinase-binding domain. Collectively, these findings have provided key insights into the mechanisms underlying the governance of peripheral CD4 T cell homeostasis and identify p27Kip1 as a target to enhance vaccine-induced CD4 T cell memory.
Related Links	http://dx.doi.org/10.4049/jimmunol.1201482
Ending Page	5128
Page Count	10
Starting Page	5119
File Format	PDF
ISSN	00221767
e-ISSN	15506606
Journal	Journal of immunology (Baltimore, Md. : 1950)
Issue Number	11
Volume Number	189
Language	English
Publisher Date	2012-12-01
Access Restriction	Open
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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