Kinetic analysis reveals potency of CD4+ CD25bright+ regulatory T-cells in kidney transplant patients

Transpl Immunol. 2007 Nov;18(2):159-65. doi: 10.1016/j.trim.2007.05.009. Epub 2007 Jun 18.

Abstract

Donor-specific hyporesponsiveness as occurs after allogeneic kidney transplantation may be mediated by repression of effector cells by a specific subset of T-cells: the CD4(+) CD25(bright+) FoxP3(+) regulatory T-cells (Tregs). Here, we examined the suppressive capacity of Tregs isolated from the leukafereses product of 6 kidney transplant recipients, by reconstituting Tregs to responder T-cells at several time-points after initiation of proliferation. We show that Tregs derived from kidney transplant patients potently restrain proliferation to donor-antigens and 3rd party-antigens in classic reconstitution assays (i.e. addition of Tregs at the start of the co-incubation). However, when Tregs were added 5 days after initiation of proliferation, they were still capable of suppressing proliferation to donor-antigens (by 38%) but no longer to 3rd party-antigens. Thus, we conclude that the potency of Tregs to suppress reactivity to specific antigens should be determined by reconstitution to ongoing reactions.

MeSH terms

  • CD4 Antigens / immunology*
  • Coculture Techniques
  • Humans
  • Interleukin-2 Receptor alpha Subunit / immunology*
  • Kidney Transplantation / immunology*
  • Lymphocyte Activation
  • Male
  • T-Lymphocytes, Regulatory / immunology*
  • Tissue Donors
  • Transplantation Tolerance

Substances

  • CD4 Antigens
  • Interleukin-2 Receptor alpha Subunit