Thesis (Ph. D.)--Illinois State University, 1990. / Title from title page screen, viewed December 2, 2005. Dissertation Committee: H. Tak Cheung (chair), Herman Brockman, Harry Huizinga, Anthony Otsuka, Brian Wilkinson. Includes bibliographical references (leaves 116-127) and abstract. Also available in print.

T cells are one of the key cells in the immune system. Although they are not the first line of defense against a pathogen, their functions can greatly enhance the phagocytosis and destruction of pathogens as well as the development of antibody responses. Furthermore, even when responding T cells have facilitated the clearance of the pathogen, they can avoid death to become long-lived cells that "remember" encountering the pathogen for years afterward. This long-term memory allows subsequent immune responses to improve with each exposure, ultimately preventing disease upon reinfection. The activation of these T cells depends on specific recognition of antigen along with a costimulatory signal. This activation process is well studied, but not completely understood. Additionally, the mechanism behind memory T cell development is still very much unknown. In the work presented in this thesis, delivery of costimulatory signals via CD4O and 0X40 were studied using an in vivo superantigen (SAg) model of T cell stimulation. In the context of this two-signal (SAg + costimulation) model, both CD4O and OX40 could deliver signals that enhanced SAg-reactive T cell clonal expansion, but they could only partially prevent T cell death. Coadministration of the inflammatory agent lipopolysaccharide (LPS), however, could keep increased responder T cell populations alive for at least two months. Interestingly, this three-signal (SAg + costimulation + LPS) induced survival was not dependent on proinflammatory cytokines or activation of the transcription factor NF-KB, but was sensitive to the immunosuppressant cyclosporin A (CsA). The mode of action of CsA may point to the mechanism driving long-term T cell survival. Additionally, examination of early time points after three-signal stimulation suggested more clues to the mechanism of survival induction. The cytokines IL-2 and TNF-�� seem to be involved early on, but for now, little is known about their complete role. Thus, the goal of this work was to investigate the costimulatory and adjuvant-mediated signals required for memory T cell development. Ultimately, an understanding of how memory T cells can be generated could be used to enhance vaccine efficacy or shut off autoimmune conditions. / Graduation date: 2002

Thesis (Ph.D.)--University of Adelaide, Dept. of Microbiology and Immunology, 1999. / Amendments page is pasted onto the front end paper. Includes bibliographical references (28 leaves).

Thesis (Ph.D.)--University of Adelaide, Dept. of Molecular Biosciences, 2002. / "January 2002" Bibliography: leaves 204-230.

Thesis (Ph. D.)--University of Texas at Austin, 2003. / Supervisor: Philip W. Tucker. Vita. Includes bibliographical references. Available also from UMI Company.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1984. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 209-232).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1983. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 199-218).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1984. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Mucosal-associated invariant T (MAIT) cells are a population of innate-like lymphocytes within the gut, liver and blood, expressing a semi-invariant T cell receptor (TCR) and high levels of the C-type lectin-like receptor, CD161. These cells recognise a metabolite of the microbial riboflavin synthesis pathway, presented by the highly conserved Major Histocompatibility Complex (MHC) class I-related protein, MR1, and are critical for the control of bacterial infections. The factors regulating the broad effector functions of MAIT cells have not been fully investigated. Utilising a novel flow cytometric killing assay, MAIT cells were shown here to require the induction of a cytotoxic phenotype through bacterial stimulation to efficiently kill target cells. Further in depth phenotypic analysis highlighted a distinct non-cytotoxic subset of CD4+ MAIT cells, with an altered cytokine-producing capacity, enriched within lymphoid tissues. Investigation into the potential role of these cells in psoriatic diseases revealed that MAIT cells within the synovial fluid of psoriatic arthritis patients are potently activated with increased IL-17 production, their frequency correlating with measures of clinical activity. MAIT cells also have an innate-like responsiveness to cytokines, a feature originally attributed to Natural Killer (NK) cells. Microarray analysis and mass cytometry experiments demonstrated that CD161 marks immature NK cells that have retained this ability to respond to innate cytokines during their differentiation, and is lost upon cytomegalovirus (CMV)-induced maturation in both healthy and human immunodeficiency virus (HIV)-infected patients. Thus, CD161 marks cells with innate-effector functions both in T cells and NK cells.

Thesis (Ph. D.)--Ohio State University, 2004. / Document formatted into pages; contains xv, 178 p. Includes bibliographical references. Abstract available online via OhioLINK's ETD Center; full text release delayed at author's request until 2006 May 20.