Project Information AT A GLANCE
Project Title: Apoptosis modulation in lymphocytes to induce immunological tolerance.
Project Objective: This project aims at developing apoptosis modulation as a novel principle for immunosuppression in solid organ transplantation of naïve and sensitized recipients, and at establishing a new effective, but less toxic protocol to induce immunological tolerance.
Project Duration and Timing: 4 years
Project Funding: • Swiss national foundation • Olga Mayenfisch Foundation
Project Partners: • Nuffield Department of Surgical Sciences, University of Oxford
• Division of Transplantation, Medical University of Vienna
Main Contact:
the end of the immune response after a viral or bacterial
infection, the immune
system generates memory T cells that are responsible for a fast recourse of the immune response in case of reinfection,” explains Cippà. “It is widely accepted that these cells are particularly resistant to immunosuppression and conditioning protocols, and are thus one of the biggest barriers to the application of low toxicity protocols in the clinical setting.”
The specificity of the Bcl-2 inhibitors
is another reason why they are such a promising prospect for tolerance protocols. “If these drugs were to cause apoptosis in other organs such as the heart or liver, then the side effects they would cause would outweigh their usefulness,” says Fehr. “Our tests on mice showed that the only areas which showed increased apoptosis were the lymphoid organs,
and in peripheral
“Approximately 95% of kidneys transplants will survive the first year. However, after this first year a constant number of organs is lost every year”
“We were particularly interested to see
what the effect of the Bcl-2 inhibitors would
have population. regulation on of It is known
these memory that
apoptosis is in
cell the
physiological regulation of memory T cells, the
very
important. We hypothesised that targeting the Bcl-2 factors would be a good way to target
the memory T cells. Our findings
showed that memory T cells are sensitive to these drugs, and we were able to overcome the memory T cell barrier using a Bcl-2 inhibitor to induce tolerance in mice.”
67
blood only lymphocytes and to some extent in the platelets, but not erythrocytes
and granulocytes were
affected by the drug.” The next step for this new protocol
will be for it to be tested in a large animal model. “Although this is not an easy step, we hope that these tests will prove to be successful so that this new protocol can eventually make its way into the clinical setting and start to make a difference to the patients who need it,” says Fehr.
★ Insight Publishers | Projects
Contact: Tel: +41 44 255 33 84 Email:
thomas.fehr@uzh.ch Web:
www.nephrologie.usz.ch/ www.physiol.uzh.ch/research/ Grwuethrich.html
Prof. Thomas Fehr MD Current positions: attending physician (Leitender Arzt) in the Division of Nephrology, University Hospital Zurich. Research group leader in the Division of Nephrology / Institute for Physiology at the University Zurich. Head of the Transplant Center, University Hospital, Zurich
Contact:
Pietro Cippà MD PhD Resident, University Hospital Zürich, Internal Medicine. Doctor in Science (PhD) from the Faculty of Science, University of Zürich.
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100 |
Page 101 |
Page 102 |
Page 103 |
Page 104 |
Page 105 |
Page 106 |
Page 107 |
Page 108 |
Page 109 |
Page 110 |
Page 111 |
Page 112 |
Page 113 |
Page 114 |
Page 115 |
Page 116 |
Page 117 |
Page 118 |
Page 119 |
Page 120 |
Page 121 |
Page 122 |
Page 123 |
Page 124 |
Page 125 |
Page 126 |
Page 127 |
Page 128 |
Page 129 |
Page 130 |
Page 131 |
Page 132