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CD4+CD25high Regulatory T Cells in the Developing Human Immune System: Implications for Pediatric HIV Infection


Although human T cells enter the peripheral lymphoid tissues early during fetal development1, the adaptive immune system in the fetus has largely been regarded as functionally immature and unresponsive to stimulation. In adults, CD4CD25high regulatory T cells (TReg) are critical for maintenance of peripheral T cell tolerance, but their role in the developing fetus is unknown. Here, we demonstrate that a large population of human fetal FOXP3CD4CD25high TReg cells, present from the earliest stages of T cell colonization of the periphery, efficiently suppresses fetal T cell responses.


Depletion of CD4+CD25high TReg cells from fetal lymph node cells, but not adult lymph nodes, resulted in the proliferation and acquisition of effector functions in the absence of exogenous stimulation by a large subpopulation of T cells identifiable by the expression of CD69 in utero. A large population of fetal CD4+CD25high TReg cells also expressed CD69+ and displayed a memory/effector phenotype, as indicated by low expression of CD45RA and CCR7. However, the CD69+ and CD69- CD4+CD25high TReg cells did not differ in their suppression of T cell responses in the absence of exogenous stimulation, indicating that the activation status of these cells do not correlate with their suppressive function.


These studies demonstrate that the fetal T cells are, in the absence CD4+CD25high TReg cells, highly responsive to stimulation, indicating that human fetal T cells are active and functionally mature. Strong evidence has also been obtained for an important role for CD4+CD25high TReg cells in controlling T cell responses in utero. The implications of these findings for pediatric HIV infection will be discussed.

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Correspondence to Joseph M McCune.

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Jakob Michaëlsson, Jeff E Mold contributed equally to this work.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Michaëlsson, J., Mold, J.E., McCune, J.M. et al. CD4+CD25high Regulatory T Cells in the Developing Human Immune System: Implications for Pediatric HIV Infection. Retrovirology 2 (Suppl 1), S107 (2005).

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