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Induction of operat...
Induction of operational tolerance to discordant dopaminergic porcine xenografts.
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Larsson, Lena C (författare)
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- Corbascio, Matthias (författare)
- Karolinska Institutet
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Pearson, Thomas C (författare)
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Larsen, Christian P (författare)
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- Ekberg, Henrik (författare)
- Lund University,Lunds universitet,Enheten för forskning kring njurfunktion och njursjukdom,Kirurgi,Forskargrupper vid Lunds universitet,Renal Research Unit,Surgery,Lund University Research Groups
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- Widner, Håkan (författare)
- Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine
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(creator_code:org_t)
- 2003
- 2003
- Engelska.
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Ingår i: Transplantation. - 1534-6080 .- 0041-1337. ; 75:9, s. 1448-1454
- Relaterad länk:
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- BACKGROUND: Porcine embryonic neural tissue transplanted intracerebrally could potentially relieve the symptoms of Parkinson's disease if the immune response toward the graft could be overcome. However, conventional immunosuppressive treatments have proven inefficient in preventing rejection. An alternative is blocking the costimulatory signals for lymphocyte activation. Treatment with cytotoxic T-lymphocyte antigen 4 immunoglobulin (CTLA4Ig) and anti-CD40L has been successful in preventing rejection of xenografts in some experimental studies, but not all. Lymphocyte function antigen (LFA)-1 is an important costimulatory molecule for CD8+ T cells, and we hypothesize that blockade with anti-LFA-1 may enhance the efficacy of CTLA4Ig and anti-CD40L therapy. METHODS: C57BL/6 mice received intracerebral transplants of ventral mesencephalic tissue from embryonic porcine donors. CTLA4Ig, anti-CD40L, and anti-LFA-1 were administered every other day on days 0 to 8, and the transplants were studied after 4 to 6 weeks. Grafts were histologically analyzed for size, survival of dopaminergic nerve cells, and immune responses. Recipients were challenged with cultured glia cells of donor origin or an allogeneic skin graft to evaluate tolerance induction. RESULTS: Mice treated with all three substances had large grafts containing high amounts of dopamine cells but a low degree of immune response. Grafts in recipients challenged with glial cells showed an increased immunologic activity but were not rejected. Triple-treated mice showed a normal rejection process of the allogeneic skin grafts. CONCLUSION: After a short course of costimulation blocking therapy, discordant neural xenografts demonstrate long-term survival, withstand immunologic challenge, yet maintain host-versus-graft reactivity. Anti-LFA-1 complements CTLA4Ig and anti-CD40L in the induction of operational tolerance to these xenografts.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
Nyckelord
- CD40 Ligand: immunology
- Brain Tissue Transplantation
- Animal
- Non-U.S. Gov't
- Swine
- Transplantation
- Inbred C57BL
- Skin Transplantation
- Support
- Heterologous: immunology
- Dopamine: analysis
- Fetal Tissue Transplantation
- Graft Survival
- Immunoconjugates: therapeutic use
- Immunosuppression: methods
- Lymphocyte Function-Associated Antigen-1: immunology
- Mesencephalon: transplantation
- Mice
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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