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|Title: ||Co-receptor and co-stimulation blockade for mixed chimerism and tolerance without myelosuppressive conditioning|
|Authors: ||Graça, Luís|
Fairchild, Paul J.
Cobbold, Stephen P
|Issue Date: ||2006|
|Publisher: ||BioMed Central|
|Citation: ||BMC Immunology 2006, 7:9|
|Abstract: ||Background: A major challenge in the application of marrow transplantation as a route to
immunological tolerance of a transplanted organ is to achieve hematopoietic stem cell (HSC)
engraftment with minimal myelosuppressive treatments.
Results: We here describe a combined antibody protocol which can achieve long-term
engraftment with clinically relevant doses of MHC-mismatched bone marrow, without the need for
myelosuppressive drugs. Although not universally applicable in all strains, we achieved reliable
engraftment in permissive strains with a two-stage strategy: involving first, treatment with anti-CD8
and anti-CD4 in advance of transplantation; and second, treatment with antibodies targeting CD4,
CD8 and CD40L (CD154) at the time of marrow transplantation. Long-term mixed chimerism
through co-receptor and co-stimulation blockade facilitated tolerance to donor-type skin grafts,
without any evidence of donor-antigen driven regulatory T cells.
Conclusion: We conclude that antibodies targeting co-receptor and co-stimulatory molecules
synergise to enable mixed hematopoietic chimerism and central tolerance, showing that neither
cytoreductive conditioning nor 'megadoses' of donor bone marrow are required for donor HSC
to engraft in permissive strains.|
|Description: ||© 2006Graca et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.|
|Peer Reviewed: ||yes|
|Appears in Collections:||FM-LIB-Artigos em Revistas Internacionais|
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