Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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
Doi: 10.1111/tri.12021
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Baranyi Ulrike
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- 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)
- anti-LFA-1
- costimulation blockade
- mixed chimerism
- rapamycin
- T memory cells
- tolerance