No description available.

Thesis (M.S.)--University of Hawaii at Manoa, 2006. / Includes bibliographical references (leaves 84-91). / ix, 91 leaves, bound ill. 29 cm

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Thesis (Ph.D.)--Michigan State University. Dept. of Pharmacology and Toxicology, 2008. / Title from PDF t.p. (viewed on Mar. 30, 2009) Includes bibliographical references (p.157-191). Also issued in print.

Dendritic Cells (DCs) are professional antigen presenting cells that play a crucial role in the induction of immune tolerance. Although DCs have been a potential target for immunotherapy, the amount of DCs in blood source is limited and ex vivo expansion has been inefficient. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) provide a great source in cell-based therapy because of their self-renewal ability and pluripotency. My project focuses on generating tolerogenic DCs (tDCs) from human pluripotent stem cells (i.e. hESCs and iPSCs) and their characterization. Specifically, hESCs and hiPSCs were first differentiated to hematopoietic progenitor cells (HPCs) using three different methods (i.e. bone-marrow stromal cell co-culture and two previously reported defined medium methods). The hESC/iPSC-differentiated hematopoietic progenitor cells (HPCs) were characterized by their surface phenotype using flow cytometry. Then the hESC/iPSC-differentiated immature DCs were further expanded and differentiated from the hESC/iPSCdifferentiated CD34+ HPCs with the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) and Interleukin 4 (IL-4). Tolerogenic properties were introduced by treating hESC-differentiated DCs with rapamycin. The treated DCs were characterized for their tolerogenicity by examining their expression of PDL1, PDL2, ICOS and CD40 etc., and their ability to promote regulatory T cells (Treg) differentiation. All these were compared with monocyte-derived tDCs. In summary, this study has examined the potential of using pluripotent stem cells-derived DCs as a cell source for immune tolerance induction therapy. / published_or_final_version / Anatomy / Master / Master of Philosophy

Thesis (Ph. D.)--University of Chicago, Division of the Biological Sciences and the Pritzker School of Medicine, June 1999. / Includes bibliographical references. Also available on the Internet.

Thesis (Ph.D.) - University of Queensland, 2004. / Includes bibliography.

No description available.

Recent developments in the expansion and manipulation of primary NK cells has allowed this source of effective anti-tumour cells to be exploited for cell-based cancer immunotherapies. While ex vivo expanded primary NK cells are highly effective in the treatment of haematological malignancies, their efficacy against the solid tumour has been limited due to the presence of immune-regulatory factors in the tumour microenvironment. These factors can abrogate NK cell function by down regulating the expression of NK activating receptors, thus preventing these highly cytotoxic effector cells from activating in response to tumour challenge. Our work explores whether the expression of a tumour specific chimeric antigen receptor (CAR) on ex vivo expanded primary NK cells would allow the lost activatory signalling to be recouped, and regain their efficacy against the solid tumour. Unfortunately, the use of primary NK cells as effectors in CAR based cell immunotherapies has been hampered by the technical limitations of producing large numbers of CAR positive primary NK cells. This has led many researchers to utilise the NK-92 cell line instead of primary cells. We demonstrate that ex vivo expanded primary CAR NK cells can be produced efficiently and demonstrate higher anti-tumour functionality than CAR NK-92. Finally, due to the intricacies of NK cell biology, they are able to effectively discriminate between healthy and malignant targets thus preventing their cytotoxic function from being directed towards the incorrect target. This could be a key advantage in the use of primary NK cells over T cells as effectors of CAR as the off-tumour/on-target adverse effects seen with CAR T cells has severely hampered this clinical strategy. We have shown that CAR T cells but not CAR NK cells are reactive towards phenotypically non-malignant, clinically relevant, healthy cells expressing the CAR target. / Thesis / Master of Science (MSc)

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related compounds are well-recognized for their immunosuppressive activity, which is mediated through an intracellular receptor and transcription factor, aryl hydrocarbon receptor (AhR). Laboratory animals exposed to TCDD are less resistant to infection and have severely impaired humoral and cell-mediated immune responses. This dissertation addressed the hypothesis that exposure to TCDD disrupts early events during the activation of CD4⁺ T cells, leading to their premature loss from the spleen. Initially, ovalbumin (OVA)-specific CD4⁺ T cells from transgenic DO11.10 mice were used to monitor the effects of TCDD on activated antigen-specific T cells. A graft-versus-host (GVH) model, in which T cells from C57B1/6 (B6) mice are injected into C57B1/6 x DBA/2 Fl (Fl) mice, was used to study the role of AhR specifically in the T cells in response to TCDD. B6 donor T cells (from AhR[superscript +/+] or AhR[superscript -/-] mice) respond to DBA/2 antigens in Fl mice and a CD4-dependent CTL response is generated. In both models, exposure to TCDD significantly decreased the number of responding CD4⁺ T cells in the spleen beginning on day 4 after initiation of the response. Exposure to TCDD altered the phenotype of OVA-specific CD4⁺ T cells beginning on day 2 after immunization with OVA. These studies also suggested that apoptosis was not the primary mechanism responsible for the loss of CD4⁺ T cells from the spleen in TCDD-treated mice. Exposure to TCDD induced AhR-dependent changes in the phenotype of B6 donor CD4⁺ T cells such that a subpopulation of CD25⁺ cells was increased in TCDD-treated Fl mice, and these cells had in vitro functional characteristics consistent with regulatory T (Treg) cells. Exposure to TCDD increased the frequency of donor CD4⁺ T cells producing interleukin (IL)-2. In addition, increased expression of CD25 in TCDD-treated mice was correlated with increased signaling through the IL-2 receptor. However, IL-2 alone was not sufficient to mimic the potent immunosuppressive effects of TCDD. These results suggest that TCDD suppresses T cell immunity in part by inducing and/or expanding a subpopulation of Treg cells by a mechanism that may involve IL-2. / Graduation date: 2006