Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Ramsey, H; Pilat, N; Hock, K; Klaus, C; Unger, L; Schwarz, C; Baranyi, U; Gattringer, M; Schwaiger, E; Wrba, F; Wekerle, T.
Anti-LFA-1 or rapamycin overcome costimulation blockade-resistant rejection in sensitized bone marrow recipients.
Transpl Int. 2013; 26(2):206-218 [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Baranyi Ulrike

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Plum Analytics:
While costimulation blockade-based mixed chimerism protocols work well for inducing tolerance in rodents, translation to preclinical large animal/nonhuman primate models has been less successful. One recognized cause for these difficulties is the high frequency of alloreactive memory T cells (Tmem) found in the (pre)clinical setting as opposed to laboratory mice. In the present study, we therefore developed a murine bone marrow transplantation (BMT) model employing recipients harboring polyclonal donor-reactive Tmem without concomitant humoral sensitization. This model was then used to identify strategies to overcome this additional immune barrier. We found that B6 recipients that were enriched with 3 × 10(7) T cells isolated from B6 mice that had been previously grafted with Balb/c skin, rejected Balb/c BM despite costimulation blockade with anti-CD40L and CTLA4Ig (while recipients not enriched developed chimerism). Adjunctive short-term treatment of sensitized BMT recipients with rapamycin or anti-LFA-1 mAb was demonstrated to be effective in controlling Tmem in this model, leading to long-term mixed chimerism and donor-specific tolerance. Thus, rapamycin and anti-LFA-1 mAb are effective in overcoming the potent barrier that donor-reactive Tmem pose to the induction of mixed chimerism and tolerance despite costimulation blockade.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Antibodies - metabolism
Antibodies, Monoclonal - therapeutic use
Bone Marrow Cells - cytology
Bone Marrow Transplantation -
CD40 Ligand - metabolism
CTLA-4 Antigen - metabolism
Chimerism -
Enzyme-Linked Immunosorbent Assay -
Flow Cytometry -
Graft Rejection -
Interferon-gamma - metabolism
Lymphocyte Function-Associated Antigen-1 - immunology
Mice -
Mice, Inbred BALB C -
Mice, Inbred C3H -
Mice, Inbred C57BL -
Sirolimus - therapeutic use
Skin Transplantation -
T-Lymphocytes - cytology
Transplantation Tolerance -

Find related publications in this database (Keywords)
costimulation blockade
mixed chimerism
T memory cells
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