Regulatory T cell development and T cell mediated tolerance

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.