title: Kinetic analysis reveals potency of CD4+ CD25bright+ regulatory T-cells in kidney transplant patients.
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.
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: J H L
authors.initials: JH
authors.lastname: Velthuis
authors.forename: D A
authors.initials: DA
authors.lastname: Hesselink
authors.forename: T K
authors.initials: TK
authors.lastname: Hendrikx
authors.forename: B J
authors.initials: BJ
authors.lastname: van der Mast
authors.forename: M
authors.initials: M
authors.lastname: Klepper
authors.forename: G E
authors.initials: GE
authors.lastname: de Greef
authors.forename: C C
authors.initials: CC
authors.lastname: Baan
authors.forename: W
authors.initials: W
authors.lastname: Weimar
mesh_terms: D015704:CD4 Antigens / Q000276:immunology*; D018920:Coculture Techniques; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014019:Tissue Donors; D023001:Transplantation Tolerance
chemical_list: D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit