Regulatory T cell development and T cell mediated tolerance

Bénard, Angèle. Regulatory T cell development and T cell mediated tolerance. 2009, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: http://edoc.unibas.ch/diss/DissB_8867

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T cell tolerance is achieved through multiple mechanisms. In this study we have tried to
characterize tolerance and T cell development in various situations. First, in the setting of bone
marrow transplantation, we could show that radioresistant T cells from immunocompetent mice
protect against the development of syngeneic graft-versus-host disease whereas
immunodeficient mice succumb to autoimmunity. However, co-injection of sorted regulatory T
cells is able to prevent the development of the disease. Second, by further investigating
radioresistant T cells in the thymus of bone marrow chimera, we could show that a small
population of host-derived DN1-2 pro-thymocytes showed similar properties of radioresistance.
Moreover, this small population is able to generate a single wave of developing T cells, which
participate in immune protection of the host before donor-derived T cells can provide protective
immune reconstitution. Third we took advantage of the protective role of regulatory T cells
during syngeneic bone marrow transplantation described above to study γ/δ T cell development
and to investigate the role of the rearranged β chain found in 15% of γ/δ T cells. We could show
that the γ/δ-derived β chain is actually indistinguishable from the β chain isolated in α/β T cells
and is able to take part in the development of fully functional α/β T cells. Finally, we have
generated double transgenic mice by expressing the agonist antigen ovalbumin in specific cell
subsets concomitantly with OVA-specific TCR. Several similar models have been previously
used to study tolerance and development of regulatory T cells. We characterized the tolerant
status of these mice and showed that the choice of the agonist along with the TCR affinity for
the same agonist is playing a significant role in the outcome of double transgenic mice.
Advisors:Rolink, Antonius G.
Committee Members:Palmer, Ed
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Developmental and Molecular Immunology (Rolink)
UniBasel Contributors:Bénard, Angèle and Rolink, Antonius G. and Palmer, Ed
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:8867
Thesis status:Complete
Number of Pages:162 Bl.
Identification Number:
edoc DOI:
Last Modified:22 Apr 2018 04:30
Deposited On:07 May 2010 06:15

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