Antigen-targeting to dendritic cells is required for engraftment of antigen-encoding bone marrow and long-term tolerance under non-myeloablative conditions

Coleman, Miranda, Thomas, Ranjeny and Steptoe, Ray (2012). Antigen-targeting to dendritic cells is required for engraftment of antigen-encoding bone marrow and long-term tolerance under non-myeloablative conditions. In: Immunology 2012 Meeting Abstracts. 99th Annual Meeting of the American Association of Immunologists, Boston, MA, United States, (). 4 -8 May 2012.

Author Coleman, Miranda
Thomas, Ranjeny
Steptoe, Ray
Title of paper Antigen-targeting to dendritic cells is required for engraftment of antigen-encoding bone marrow and long-term tolerance under non-myeloablative conditions
Conference name 99th Annual Meeting of the American Association of Immunologists
Conference location Boston, MA, United States
Conference dates 4 -8 May 2012
Proceedings title Immunology 2012 Meeting Abstracts   Check publisher's open access policy
Journal name Journal of Immunology   Check publisher's open access policy
Place of Publication Bethesda, MD, United States
Publisher American Association of Immunologists
Publication Year 2012
Sub-type Published abstract
ISSN 0022-1767
1550-6606
Volume 188
Total pages 1
Language eng
Abstract/Summary Transplantation of hematopoietic stem cells (HSC) or bone marrow (BM) engineered to encode antigens is a means of inducing antigen-specific tolerance that might be suitable for ‘turning off’ pathogenic effector and memory T-cell responses. However, transplantation into primed hosts under non-myeloablative conditions could lead to rejection of engineered HSC or BM. We hypothesized targeting antigen expression to mature APC would alleviate rejection of engineered HSC while still permitting expression in the ‘tolerogenic’ cells that arise after transplantation. Using non-myeloablative conditions, we compared engraftment and ‘tolerogenicity’ in naïve or immune hosts of BM encoding an antigen that was ubiquitously expressed, targeted to diverse APC, or targeted to DC. When antigen was expressed ubiquitously, engraftment failed (<1%) but targeting antigen to DC, permitted high levels of BM engraftment ({asymp}40%). Unexpectedly, BM failed to engraft (<1%) when antigen was targeted using a MHC class II promoter. This was due low level MHC class II expression by HSC leading to antigen expression and subsequent immune rejection of engrafting HSC. Long-term tolerance of antigen-specific memory T cells occurred only when engraftment was facilitated by targeting antigen to DC. For clinical translation, careful selection for a promoter that optimally targets DC will be imperative to ensure engraftment of antigen-encoding cells and long-term tolerance.
Q-Index Code CX
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Conference Paper
Collections: Temporary Review
UQ Diamantina Institute Publications
 
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