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+CD25bright+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.

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Keywords Human, Kidney transplantation, Regulatory T-cells
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Veldhuis, J.H.L., Hesselink, D.A., Hendrikx, T.K., van der Mast, B.J., Klepper, M., de Greef, G.E., … Weimar, W.. (2007). Kinetic analysis reveals potency of CD4+ CD25bright+ regulatory T-cells in kidney transplant patients. Transplant Immunology, 18(2), 159–165. doi:10.1016/j.trim.2007.05.009