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CD4 + CD25 bright+ Regulatory T Cells Can Mediate Donor Nonreactivity in Long‐Term Immunosuppressed Kidney Allograft Patients
Author(s) -
Velthuis J. H. L.,
Mol W. M.,
Weimar W.,
Baan C. C.
Publication year - 2006
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2006.01566.x
Subject(s) - foxp3 , medicine , azathioprine , immunology , population , transplantation , kidney , il 2 receptor , mycophenolate , kidney transplantation , prednisone , t cell , immune system , disease , environmental health
CD4 + CD25 bright+ FoxP3 + T cells are potent regulators of T‐cell reactivity, but their possible involvement in donor‐specific nonresponsiveness after clinical kidney transplantation remains to be elucidated. We assessed the proliferative donor‐reactivity in 33 kidney allograft recipients who were maintained on a combination of proliferation inhibitors (mycophenolate mofetil (MMF) or Azathioprine (Aza)) and prednisone, long (>5 years) after transplantation. Of the 33 patients, 8 still exhibited donor‐reactivity, whereas 25 were classified as donor nonreactive patients. Within these 25 donor nonreactive patients, we assessed the involvement of CD4 + CD25 bright+ regulatory T cells both by depleting them from the responder population as well as by reconstituting them to the CD25 −/dim effector population. The absence of proliferation in these 25 patients, was abolished in 7 (28%) recipients upon depletion of the CD4 + CD25 bright+ T cells. Reconstitution of these cells suppressed the donor‐reactivity in a dose‐dependent manner. Adding‐back CD4 + CD25 bright+ T cells inhibited the anti‐third party response in all recipients, indicating that functional CD4 + CD25 bright+ T cells circulate despite more then 5 years of immunosuppressive treatment.Altogether, we conclude that in long‐term immunosuppressed kidney allograft patients functional regulatory CD4 + CD25 bright+ T cells circulate but that these cells mediate donor non reactivity only in a subset of patients.