Thesis--Wisconsin. / Vita. Bibliography; leaves 124-129.

abstract / Orthopaedics and Traumatology / Doctoral / Doctor of Philosophy

No description available.

No description available.

Clinical transplantation continues to rely on the use of non-specific immunosuppressive therapy, which reduces the incidence of graft rejection but also carries with it undesirable side effects such as infection and malignancy. A preferable option would be to induce operational graft tolerance without the need for such non-specific therapy, for example by harnessing natural mechanisms. In recent years there has been much progress in the characterisation of CD4⁺ cells that possess suppressive or regulatory properties in experimental systems; particular attention has been focussed upon CD4⁺ cells expressing CD25, the α subunit of the IL-2 receptor, which have been shown to possess regulatory capacity both in vitro and in vivo in autoimmune disease and transplantation models. The aim of this study was to examine the potential role of CD4⁺CD25⁺ regulatory T cells (Treg) in the induction phase of tolerance in a transplantation model. Pre-treatment of mice with fully allogeneic blood administered under the cover of anti-CD4 antibody is shown to lead to the generation of CD4⁺CD25⁺ cells capable of preventing the rejection of donor type, but not third party, skin allografts mediated by CD4⁺CD45RB^high cells in secondary recipients. In addition to their suppressive properties in vivo, these CD4⁺CD25⁺ cells also display the ability to regulate the proliferation of target T cell populations in vitro. Generation of CD4⁺CD25⁺ Treg by the pre-treatment protocol is not reliant upon an intrathymic selection process nor upon the expansion of a pre-existing CD4⁺CD25⁺ Treg population, but can occur through the conversion of peripheral CD4⁺CD25^- cells to a regulatory phenotype. Although the regulatory function of the CD4⁺CD25⁺ cells generated by pre-treatment is donor strain-specific in vivo, this specificity can be overcome by activating the cells before their regulatory capacity is tested. Moreover, CD4⁺CD25⁺ cells generated by pre-treatment with a non-cellular protein antigen completely unrelated to the graft can also regulate skin allograft rejection provided that these Treg are first activated. It is hoped that the principles defined by these findings identify a strategy that may be applicable in clinical transplantation and in the therapy of autoimmune disease.

Bibliography: leaves 206-254. / xiii, 254 leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Analyses the cytokine gene expression and the manipulation of these responses in order to offer some insights into the Th1 and Th2 responses associated with allograft rejection. Supports the concept that the unmodified alloimmune response involves complex interactions between Th1-like, Th2-like and APC-derived cytokines. Immunomodulation of the alloimmune response is associated with the down regulation of multiple cytokines within both Th1 and Th2 populations with concurrent upregulation of IL-10 expression. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1998?

Bibliography: leaves 206-254. / xiii, 254 leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Analyses the cytokine gene expression and the manipulation of these responses in order to offer some insights into the Th1 and Th2 responses associated with allograft rejection. Supports the concept that the unmodified alloimmune response involves complex interactions between Th1-like, Th2-like and APC-derived cytokines. Immunomodulation of the alloimmune response is associated with the down regulation of multiple cytokines within both Th1 and Th2 populations with concurrent upregulation of IL-10 expression. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1998?

Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1998? / Bibliography: leaves 206-254.

The populations of cells which infiltrate tissue allografts in W mutant mice and their non-mutant littermates were investigated using the light and electron microscopes. Initially, thyroid allografts were attempted but this tissue proved unsatisfactory for comparative studies and skin was used instead. The cells infiltrating the skin grafts were isolated enzymatically and characterized using the light microscope. In addition, cells in epon sections of skin grafts were identified using the electron miscroscope. The frequency of the various cell types isolated from grafts in mutant mice differed significantly from that of cells isolated from grafts in non-mutant mice. The electron microscope studies indicated that the cell types infiltrating skin allografts are the same in both mutant and non-mutant hosts. / Science, Faculty of / Zoology, Department of / Graduate

No description available.