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

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-2R beta(-/-) mice, only a small fraction of donor Treg 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-2R beta(-/-) 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.