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"CHARACTERIZATION OF VIRUS-ACTIVATED HUMAN PLASMACYTOID DENDRITIC CELLS: IMPLICATIONS FOR GENERATING EFFECTIVE IMMUNE RESPONSES"

by
Temitayo Awoyomi
Molecular Pathology and Immunology Program
B.A. 2007, Lehman College, CUNY, NY


Thesis Advisor: Patricia Fitzgerald-Bocarsly, Ph.D.
Professor
Department of Pathology and Laboratory Medicine

Wednesday, April 10, 2013
10.00 A.M., MSB C-600


Abstract

Viral activation of human plasmacytoid dendritic cells (pDC) leads to production of copious amounts of interferon alpha (IFN-). These activated cells also undergo phenotypic changes that translate into various functions as the cells mature into antigen presenting cells (APC). Proteins like CD40 (activation), CD80, CD86, HLADR (stimulation and co-stimulation), CD83 (maturation), CD62L, CCR7, CXCR4, CCR5 (trafficking/HIV-co-receptors), PD-L1 (CD8+ cell activator) and OX40L (Th2 activator) were studied. We investigated whether the same pDC that produce IFN- also modulate these surface receptors or whether they represent distinct subpopulations with varying activation profiles.
On stimulation of pDC with HSV-1 or HIV-MN AT2, we observed a time-dependent increase in the expression of these functional receptors, IFN- and also co-expression of these receptors and IFN-. We also observed a time-dependent down-regulation of the trafficking molecule L-selectin (CD62L) as pDC produced IFN- in response to HSV and HIV. Kinetics of pDC activation were slightly slower with HIV stimulation as compared to HSV stimulation. A sub-population of pDC was also observed to only express these functional receptors or IFN-. It is unclear whether this sub-population of pDC performs a single function or whether these were captured along a continuum, i.e., pDC that start out producing IFN- them mature into non-IFN-producing antigen presenting cells.
Functional studies demonstrated that when activated pDC that were IFN- positive were co-cultured with CD4 T cells, proliferation was observed as compared to minimal or no proliferation upon co-culture with IFN- negative pDC. Our findings suggest that not only is IFN- co-expressed with receptors important for activation and maturation of T cells, but that the IFN- positive cells that activate T cells express higher levels of these functional receptors, some of which have opposing functions, pointing to a more complex modulation of T cell activation than previously appreciated.


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