Functional CD25(bright+) alloresponsive T cells in fully immunosuppressed renal allograft recipients.

Full Abstract

BACKGROUND:
Evidence from animal studies indicate a crucial role for CD25(bright+) regulatory T cells in transplantation tolerance.

METHODS:
To assess whether peripheral CD25(bright+) T cells control immune responses in immunosuppressed kidney transplant patients, we analyzed the suppressive capacities of these cells using mixed lymphocytes reactions.

RESULTS:
Allogeneic stimulation of patients peripheral blood mononuclear cells was associated with IL-2 production and T-cell proliferation. Depletion of CD25(bright+) T cells resulted in a 35% (median) higher IL-2 production and a 38% higher proliferative response against third party cells, showing that functional regulatory CD25(bright+) T cells were present (p = 0.03 and 0.02 respectively). In eight out of 11 patients, we also demonstrated regulation activity against donor-activated T cells (p = 0.03). These data were confirmed in coculture experiments with isolated CD25(-/dim) T cells plus CD25(bright+) T cells. At a 1:2 ratio, the CD25(bright+) T cells suppressed the proliferation of CD25(-/dim) donor- and third party-stimulated responder T cells.

CONCLUSIONS:
CD25(bright+) T cells with immune regulatory activities against anti-donor-responsive T cells are readily detectable in renal allograft recipients during treatment with full dosage immunosuppression. Whether CD25(bright+) T cells indeed play a role in graft acceptance after organ transplantation in patients remains to be elucidated.

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Author information

Author/s: Baan, Carla C (CC); Velthuis, Jurjen H L (JH); van Gurp, Evelien A F J (EA); Mol, Wendy M (WM); Klepper, Mariska (M); Ijzermans, Jan N M (JN); Weimar, Willem (W);

Affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. c.c.baan(-atsign-)erasmusmc.nl

Journal and publication information

Publication Type: Journal Article

Journal: Clinical transplantation (Clin Transplant), published in Denmark. (Language: eng)

Reference: -2007 Jan-Feb; vol 21 (issue 1) : pp 63-71

Dates: Created 2007/02/16; Completed 2007/04/04;

PMID: 17302593, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Antigens, CD - immunology
CD4-Positive T-Lymphocytes - immunology
Humans
Immunosuppressive Agents - therapeutic use
Interleukin-2 - biosynthesis; immunology
Interleukin-2 Receptor alpha Subunit - genetics; immunology

Kidney Transplantation - immunology
Lymphocyte Culture Test, Mixed
Lymphocyte Depletion
Polymerase Chain Reaction
T-Lymphocytes - immunology
Transplantation, Homologous - immunology

Associated Chemicals: Antigens, CD (0) ; Immunosuppressive Agents (0) ; Interleukin-2 (0) ; Interleukin-2 Receptor alpha Subunit (0)

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