CD4+CD25+ FOXP3+ regulatory T cells from human thymus and cord blood suppress antigen-specific T cell responses

Kajsa Wing, Pia Larsson, Kerstin Sandström, Samuel B. Lundin, Elisabeth Suri-Payer, Anna Rudin

Research output: Contribution to journalArticleResearchpeer-review

85 Citations (Scopus)

Abstract

Activation of self-reactive T cells in healthy adults is prevented by the presence of autoantigen-specific CD4+CD25+ regulatory T cells (CD25+ Treg). To explore the functional development of autoantigen-reactive CD25+ Treg in humans we investigated if thymic CD25+ Treg from children aged 2 months to 11 years and cord blood CD25+ Treg are able to suppress proliferation and cytokine production induced by specific antigens. While CD4+CD25- thymocytes proliferated in response to myelin oligodendrocyte glycoprotein (MOG), tetanus toxoid and beta-lactoglobulin, suppression of proliferation was not detected after the addition of thymic CD25+ Treg. However, CD25+ Treg inhibited interferon (IFN)-γ production induced by MOG, which indicates that MOG-reactive CD25+ Treg are present in the thymus. In contrast, cord blood CD25+ Treg suppressed both proliferation and cytokine production induced by MOG. Both cord blood and thymic CD25+ Treg expressed FOXP3 mRNA. However, FOXP3 expression was lower in cord blood than in thymic CD25+ T cells. Further characterization of cord blood CD25+ T cells revealed that FOXP3 was highly expressed by CD25+CD45RA+ cells while CD25+CD45RA- cells contained twofold less FOXP3, which may explain the lower expression level of FOXP3 in cord blood CD25 + T cells compared to thymic CD25+ T cells. In conclusion, our data demonstrate that low numbers of MOG-reactive functional CD25 + Treg are present in normal thymus, but that the suppressive ability of the cells is broader in cord blood. This suggests that the CD25+ Treg may be further matured in the periphery after being exported from the thymus.

Original languageEnglish
Pages (from-to)516-525
Number of pages10
JournalImmunology
Volume115
Issue number4
DOIs
Publication statusPublished - 1 Aug 2005
Externally publishedYes

Keywords

  • CD25 regulatory T cells
  • Cord blood
  • Myelin oligodendrocyte glycoprotein
  • Thymus

Cite this