Date of Award

Summer 8-1-2016

Degree Type

Dissertation

Degree Name

PhD Molecular Bioscience

Department

Biology

Advisor

Heping Zhou, Ph.D

Committee Member

Michael Shaw, Ph.D

Committee Member

Constantine Bitsaktsis, Ph.D

Committee Member

Allan Blake, Ph.D

Committee Member

Jane Ko, Ph.D

Keywords

Immunology, Leukocytes, Dendritic Cells, Toll-like Receptors

Abstract

Dendritic cells (DCs) represent a population of innate immune cells that are highly efficient at promoting immune responses. DCs are capable of presenting antigens to both CD4 and CD8 T cells. DC presentation and interaction with T cells can result in either immune stimulation or tolerance. This study intends to phenotype a rare subset of DCs found in the human blood and is distinguishable by the expression of various surface markers including: lineage markers (Lin), HLADR, CD1c, and CD141 or BDCA-3. Stimulating BDCA-3 DCs with Poly I:C, a toll-like receptor (TLR) 3 agonist, resulted in the up-regulation of various canonical activation markers such as CD40, CD80, and CD86 as well as immunoglobulin-like transcript (ILT) 3 and 4 as measured by flow cytometry. ILTs are novel surface molecules with implicated inhibitory functions and are selectively expressed by APCs, such as DCs. The surface induction of ILT3 and ILT4 occurred in both time- and dose-dependent manner. The up-regulation of ILT3 and ILT4 within the BDCA-3 subset of DCs resulted in the unexpected formation of various subsets of BDCA-3 DCs expressing: ILT3- ILT4-, ILT3- ILT4+, ILT3+ ILT4-, and ILT3+ ILT4+. Due to limited numbers of cells, we focused our efforts to determine the biological differences between ILT3---ILT4- and -ILT4+ BDCA-3 DCs after Poly I:C stimulation. This study will show that these two populations of BDCA-3 DCs differ in their cytokine secretion profile, genomic signature, and their ability to prime allogenic naïve T cells.

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