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

Robb, R.J., Lineburg, K.E., Kuns, R.D., Wilson, Y.A., Raffelt, N.C., Olver, S.D., Varelias, A., Alexander, K.A., Teal, B.E., Sparwasser, T., Hammerling, G.J., Markey, K.A., Koyama, M., Clouston, A.D., Engwerda, C.R., Hill, G.R. and MacDonald, K.P.A. (2012) Identification and expansion of highly suppressive CD8 +FoxP3 + regulatory T cells after experimental allogeneic bone marrow transplantation. Blood, 119 24: 5898-5908. doi:10.1182/blood-2011-12-396119


Author Robb, R.J.
Lineburg, K.E.
Kuns, R.D.
Wilson, Y.A.
Raffelt, N.C.
Olver, S.D.
Varelias, A.
Alexander, K.A.
Teal, B.E.
Sparwasser, T.
Hammerling, G.J.
Markey, K.A.
Koyama, M.
Clouston, A.D.
Engwerda, C.R.
Hill, G.R.
MacDonald, K.P.A.
Title Identification and expansion of highly suppressive CD8 +FoxP3 + regulatory T cells after experimental allogeneic bone marrow transplantation
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
Publication date 2012-06-14
Sub-type Article (original research)
DOI 10.1182/blood-2011-12-396119
Open Access Status
Volume 119
Issue 24
Start page 5898
End page 5908
Total pages 11
Place of publication Washington, DC, U.S.A.
Publisher American Society of Hematology
Language eng
Subject 2720 Hematology
1303 Specialist Studies in Education
1307 Cell Biology
2403 Immunology
Abstract 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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