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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4216-4221.
Prepublished online as a Blood First Edition Paper on February 19, 2004; DOI 10.1182/blood-2004-01-0005.
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IMMUNOBIOLOGY
Induction of antigen-specific tolerance to bone marrow allografts with CD4+CD25+ T lymphocytes
Olivier Joffre,
Nathalie Gorsse,
Paola Romagnoli,
Denis Hudrisier, and
Joost P. M. van Meerwijk
From the Tolerance and Autoimmunity Section, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie de Toulouse Purpan, Institut Claude de Preval, Toulouse, France; Faculty of Life-Sciences (UFR-SVT), University Toulouse III, Toulouse, France; and Institut Universitaire de France.
Thymus-derived regulatory T lymphocytes of CD4+CD25+ phenotype regulate a large variety of beneficial and deleterious immune responses and can inhibit lethal graft-versus-host disease in rodents. In vitro, CD4+CD25+ T cells require specific major histocompatibility complex (MHC)/peptide ligands for their activation, but once activated they act in an antigen-nonspecific manner. In vivo, regulatory T cells are also activated in an antigen-specific fashion, but nothing is known about antigen specificity of their suppressor-effector function. Here we show that CD4+CD25+ regulatory T lymphocytes isolated from naive mice and activated in vitro with allogeneic antigen-presenting cells (APCs) induced specific long-term tolerance to bone marrow grafts disparate for major and minor histocompatibility antigens; whereas "target" bone marrow was protected, third-party bone marrow was rejected. Importantly, in mice injected with a mix of target and third-party bone marrows, protection and rejection processes took place simultaneously. These results indicate that CD4+CD25+ regulatory T cells can act in an antigen-specific manner in vivo. Our results suggest that CD4+CD25+ regulatory T cells could in the future be used in clinical settings to induce specific immunosuppression. (Blood. 2004;103:4216-4221)
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