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  • Oral presentation
  • Open Access

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

  • Jakob Michaëlsson1,
  • Jeff E Mold1,
  • Joseph M McCune1, 2, 3Email author and
  • Douglas F Nixon1, 2, 3
Contributed equally
Retrovirology20052(Suppl 1):S107

https://doi.org/10.1186/1742-4690-2-S1-S107

Published: 8 December 2005

Keywords

Cell ResponseTReg CellEffector FunctionHuman ImmuneAdaptive Immune System

Background

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.

Results

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.

Conclusion

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.

Notes

Authors’ Affiliations

(1)
Gladstone Institute of Virology and Immunology, University of California, San Francisco, USA
(2)
Department of Medicine, University of California, San Francisco, USA
(3)
These authors are equal last authors, USA

Copyright

© The Author(s) 2005

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