Essential role for interleukin-2 for CD4+CD25+ T regulatory cell development during the neonatal period

doi:10.1084/jem.20041179

Published 7 March 2005. doi:10.1084/jem.20041179
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 5, 769-777

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Essential role for interleukin-2 for CD4⁺CD25⁺ T regulatory cell development during the neonatal period

Allison L. Bayer, Aixin Yu, Dennis Adeegbe, and Thomas R. Malek

Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33136

CORRESPONDENCE Thomas R. Malek: tmalek{at}med.miami.edu

Although many aspects of CD4⁺CD25⁺ T regulatory (T_reg) celldevelopment remain largely unknown, signaling through the IL-2Rrepresents one feature for the production of T_reg cells. Therefore,the present study was undertaken to further define early developmentalsteps in the production of T_reg cells, including a more preciseview on the role of interleukin (IL)-2 in this process. Afteradoptive transfer of wild-type T_reg cells into neonatal IL-2Rß^–/–mice, only a small fraction of donor T_reg cells selectivelyseeded the lymph node (LN). These donor T_reg cells underwentrapid and extensive IL-2–dependent proliferation, followedby subsequent trafficking to the spleen. Thus, IL-2 is essentialfor T_reg cell proliferation in neonatal LN. The number and distributionof T_reg cells in the periphery of normal neonatal mice closelyparalleled that seen for IL-2Rß^–/– micethat received T_reg cells. However, for normal neonates, blockadeof IL-2 decreased T_reg cells in both the thymus and LN. Therefore,two steps of T_reg cell development depend upon IL-2 in neonatalmice, thymus production, and subsequent expansion in the LN.

Abbreviations used in this paper: APC, allophycocyanin; CFSE,5-(and 6-)carboxyfluorescein diacetate, succinimidyl ester;cyc, Cy-chrome; GITR, glucocorticoid-induced TNF receptor; PerCP,peridinin chlorophyll- ${alpha}$ protein; T_reg, T regulatory.

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