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Prepublished online as a Blood First Edition Paper on May 29, 2003; DOI 10.1182/blood-2003-04-1164.

Submitted April 15, 2003
Accepted May 19, 2003
Induction of allopeptide-specific human CD4+CD25+ regulatory T cells ex-vivo
Shuiping Jiang, Niels Camara, Giovanna Lombardi, and Robert I Lechler*
Department of Immunology, Imperial College, London, United Kingdom
* Corresponding author; email: r.lechler{at}imperial.ac.uk.
Although CD4+CD25+ regulatory T cells are pivotal in the prevention of autoimmunity and appear to mediate transplantation tolerance, little is known concerning their antigen-specificity. Here we describe the induction of a human CD4+CD25+ regulatory T cell line specific for a defined peptide alloantigen (HLA-A2 138-170) by priming purified CD4+CD25+ cells ex-vivo. The regulatory cells were anergic and retained their ability to suppress antigen-driven responses of CD4+CD25- cells. They inhibited not only IL-2 secretion by CD4+CD25- T cells specific for the same peptide, but also direct alloresponse of naive CD4+CD25- T cells stimulated by semi-allogeneic dendritic cells (DCs) in the presence of the peptide ("linked suppression"). They also suppressed the response of CD4+ T cells specific for viral and bacterial antigens. The suppressive T cell line showed sustained high CD25 expression. These findings suggest that peripheral CD4+CD25+ regulatory cells are a precommitted cell lineage from which cells with specificity for non-self-peptides can be selected. This may pave the way for inducing and expanding peptide antigen-specific regulatory T cells ex-vivo for cell therapy in transplantation, allergy and autoimmune disease.

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