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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) cell development remain largely unknown, signaling through the IL-2R represents one feature for the production of T_reg cells. Therefore, the present study was undertaken to further define early developmental steps in the production of T_reg cells, including a more precise view on the role of interleukin (IL)-2 in this process. After adoptive transfer of wild-type T_reg cells into neonatal IL-2Rß^–/– mice, only a small fraction of donor T_reg cells selectively seeded the lymph node (LN). These donor T_reg cells underwent rapid and extensive IL-2–dependent proliferation, followed by subsequent trafficking to the spleen. Thus, IL-2 is essential for T_reg cell proliferation in neonatal LN. The number and distribution of T_reg cells in the periphery of normal neonatal mice closely paralleled that seen for IL-2Rß^–/– mice that received T_reg cells. However, for normal neonates, blockade of 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 neonatal mice, 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- protein; T_reg, T regulatory.

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