Cutting Edge: Foxp3-mediated Induction of Pim 2 Allows Human T Regulatory Cells to Preferentially Expand in Rapamycin

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2008 Apr 22

PMID 18424697

Citations 86

Authors

Samik Basu

Tatiana Golovina

Tatiana Mikheeva

Carl H June

James L Riley

Affiliations

Soon will be listed here.

Abstract

Addition of rapamycin to cultures of expanding natural CD4+CD25+Foxp3+ T regulatory cells (Tregs) helps maintain their suppressive activity, but the underlying mechanism is unclear. Pim 2 is a serine/threonine kinase that can confer rapamycin resistance. Unexpectedly, pim 2 was found to be constitutively expressed in freshly isolated, resting Tregs, but not in CD4+CD25- T effector cells. Introduction of Foxp3, but not Foxp3Delta2, into effector T cells induced pim 2 expression and conferred preferential expansion in the presence of rapamycin, indicating that Foxp3 can regulate pim 2 expression. Finally, we determined there is a positive correlation between Treg expansion and Foxp3 expression in the presence of rapamycin. Together, these results indicate that Tregs are programmed to be resistant to rapamycin, providing further rationale for why this immunosuppressive drug should be used in conjunction with expanded Tregs.

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