Identification and expansion of highly suppressive CD8(+)FoxP3(+) regulatory T cells after experimental allogeneic bone marrow transplantation.

Journal article

FoxP3(+) confers suppressive properties and is confined to regulatory T cells (T(reg)) that potently inhibit autoreactive immune responses. In the transplant setting, natural CD4(+) T(reg) are critical in controlling alloreactivity and the establishment of tolerance. We now identify an important CD8(+) population of FoxP3(+) T(reg) that convert from CD8(+) conventional donor T cells after allogeneic but not syngeneic bone marrow transplantation. These CD8(+) T(reg) undergo conversion in the mesenteric lymph nodes under the influence of recipient dendritic cells and TGF-β. Importantly, this population is as important for protection from GVHD as the well-studied natural CD4(+)FoxP3(+) population and is more potent in exerting class I-restricted and antigen-specific suppression in vitro and in vivo. Critically, CD8(+)FoxP3(+) T(reg) are exquisitely sensitive to inhibition by cyclosporine but can be massively and specifically expanded in vivo to prevent GVHD by coadministering rapamycin and IL-2 antibody complexes. CD8(+)FoxP3(+) T(reg) thus represent a new regulatory population with considerable potential to preferentially subvert MHC class I-restricted T-cell responses after bone marrow transplantation.

Authors: Robb, R; Lineburg, K; Kuns, R; Wilson, Y; Raffelt, N

• Publication status: Published
• Journal: Blood
• Volume: 119
• Issue: 24
• Pages: 5898-5908
• Publication date: 2012-06-01
• DOI: 10.1182/blood-2011-12-396119
• EISSN: 1528-0020
• ISSN: 0006-4971
• Language: English
• Keywords: Animals; Cell Proliferation; Cell Differentiation; Lymph Nodes; Interleukin-2; Forkhead Transcription Factors; CD8-Positive T-Lymphocytes; Immune Tolerance; Transforming Growth Factor beta; Sirolimus; Epitopes; T-Lymphocytes, Regulatory; Mice, Inbred C57BL; Female; Dendritic Cells; Mice; Antibodies; Survival Analysis; Bone Marrow Transplantation; Transplantation, Homologous; Graft vs Host Disease; Phenotype