The Role Of Il-22 Produced By Th17 Cells In Type 1 Diabetes, Stacey M. Bellemore

Electronic Thesis and Dissertation Repository

Interleukin-22 (IL-22) is produced by T helper 17 (Th17) cells. Th17 cells have been shown to be pathogenic in autoimmune diseases, however their role in type 1 diabetes (T1D) remains controversial. We have shown that Th17-differentiation of naïve T cells can be driven by IL-23 + IL-6 to produce large amounts of IL-22 and induce T1D. Conversely, polarizing T cells using TGF-β + IL-6 led to nonpathogenic Th17 cells that produced lower IL-22 levels. We have shown that neutralizing IFN-γ during polarization leads to a drastic increase in IL-22. We have also found IL-22-producing cells in the pancreas of diabetic …

Role Of Inos In Septic Pulmonary Microvascular Endothelial Cell Activation, Zahra Asad

Electronic Thesis and Dissertation Repository

Abstract

Background. Neutrophils and nitric oxide (NO) derived from inducible NO synthase (iNOS) contributes importantly to the pathophysiology of acute lung injury (ALI) and pulmonary microvascular endothelial cell (PMVEC) injury. However, the mechanism of neutrophil and neutrophil iNOS dependent PMVEC injury has not been addressed. In our studies, we assessed PMVEC activation under septic conditions, and defined the role of PMVEC vs. bone-marrow polymorphonuclear leukocytes (PMN) iNOS in this septic PMVEC activation.

Methods and Results. We isolated PMVEC from iNOS+/+ and iNOS-/- mice lungs magnetically by microbeads attached to anti-PECAM antibodies, sorted by flow cytometry (FACS) by DiI-acetylated low density …

Bioengineering The Expression Of Active Recombinant Human Cathepsin G, Enteropeptidase, Neutrophil Elastase, And C-Reactive Protein In Yeast, Eliot T. Smith

Electronic Theses and Dissertations

The yeasts Pichia pastoris and Kluyveromyces lactis were used to express several recombinant human proteins for further biochemical characterization. Two substitution variants of recombinant human enteropeptidase light chain (rhEPL) were engineered to modify the extended substrate specificity of this serine protease. Both were secreted as active enzymes in excess of 1.7 mg/L in P. pastoris fermentation broth. The substitution variant rhEPL R96Q showed significantly reduced specificities for the preferred substrate sequences DDDDK and DDDDR; however, the rhEPL Y174R variant displayed improved specificities for these substrate sequences relative to all other reported variants of this enzyme. The neutrophil serine proteases human …

T-Cell Treatments For Solid And Hematological Tumors, Drew C. Deniger

Dissertations & Theses (Open Access)

Cell-based therapies have demonstrated potency and efficacy as cancer treatment modalities. T cells can be dichotomized by their T cell receptor (TCR) complexes where alpha/beta T cells (95% of T cells) and gamma/delta T cells (+T cells proliferated to clinically significant numbers and ROR1⁺ tumor cells were effectively targeted and killed by both ROR1-specific CAR⁺ T cell populations, although ROR1RCD137 were superior to ROR1RCD28 in clearance of leukemia xenografts in vivo. The second specific aim focused on generating bi-specific CD19-specific CAR⁺ gamma/delta T cells with polyclonal TCRgamma/delta repertoire on CD19⁺ artificial antigen presenting cells (aAPC). …

Modulating T Cell Responses To Control Stromal Keratitis, Tamara Antia Veiga Parga

Doctoral Dissertations

Herpetic stromal keratitis (SK) is an immunoinflammatory corneal lesion caused by herpes simplex virus (HSV) infection. This infection, in some cases, can result in a chronic immunoinflammatory lesion that is the most common cause of infectious blindness in the developed world. Studies in animal models have revealed that SK lesions are orchestrated mainly by IFN-gamma producing CD4+ T cells (Th1) and neutrophils that infiltrate the corneal stroma.

The first part of this dissertation (I) reviews literature on HSV induced corneal SK immunopathology and the role of Tregs in viral infections. It also focuses on the understanding of HSV-1 induced immunoinflammatory …

Stimulation Through Tlr4 Increases Fviii Inhibitor Formation In A Mouse Model Of Hemophilia A, Claire K. Holley

Dissertations & Theses (Open Access)

Hemophilia A is a clotting disorder caused by functional factor VIII (FVIII) deficiency. About 25% of patients treated with therapeutic recombinant FVIII develop antibodies (inhibitors) that render subsequent FVIII treatments ineffective. The immune mechanisms of inhibitor formation are not entirely understood, but circumstantial evidence indicates a role for increased inflammatory response, possibly via stimulation of Toll-like receptors (TLRs), at the time of FVIII immunization. I hypothesized that stimulation through TLR4 in conjunction with FVIII treatments would increase the formation of FVIII inhibitors. To test this hypothesis, FVIII K.O. mice were injected with recombinant human FVIII with or without concomitant doses …

What Is The Effectiveness Of Roxithromycin In Management Of The Signs And Symptoms Of Rheumatoid Arthritis?, Adriana Distanislao

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not roxithromycin is effective in management of the signs and symptoms of rheumatoid arthritis.

STUDY DESIGN: Review of three primary studies in the English language published in 2006, 2009, and 2011.

DATA SOURCES: Randomized, controlled and double blind clinical trials testing the effectiveness roxithromycin in management of inflammation and signs and symptoms of rheumatoid arthritis were found using the PubMed and Ovid databases.

OUTCOMES MEASURED: Improvement in the signs and symptoms of tenderness/inflammation using the American College of Rheumatology-20 (ACR-20) scoring approach, improvement of quality of …

Generation And Characterization Of Peptide Fusion Proteins, Brianna L. Probasco

Graduate School of Biomedical Sciences Theses and Dissertations

Pathogenic Th17 cells drive progression of many autoimmune diseases. Th17 cells develop from naïve T cells in the immune system after antigen-driven stimulation in a specific cytokine environment. Normally, T cells act to fight off infection, but when not properly controlled, they can cause disease. The cytokine interleukin-23 (IL-23) plays an essential role in the expansion of pathogenic Th17 cells. IL-23 is a heterodimeric protein, composed of a p19 alpha chain and a p40 beta chain. The p40 is also part of IL-12 and binds to the IL-12 receptor beta 1 (IL-12Rβ1) subunit. Thus, it follows that the IL-23 receptor …