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Regulation of dendritic cell biology in vitro and in vivo with biological response modifiers.

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Call No.	QR185.8.D45 F75 2004
Author	Frleta, Davor.
Title	Regulation of dendritic cell biology in vitro and in vivo with biological response modifiers.
Date	2004
Abstract	Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that regulate antigen-specific T cell activation or tolerance. The maturation state of DCs is critical since immature DCs are believed to induce T cell tolerance whereas mature DCs stimulate T cell activation. DC maturation is primarily characterized by decreased antigen-uptake and up-regulation of MHC class I, II, and costimulatory molecules necessary for T cell activation. Many different stimuli induce DC maturation either in vitro or in vivo. The goal of these studies is to extend our understanding of DC biology in vitro and in vivo in response to different biological response modifiers. These studies reveal differences in expression kinetics of MHC class II and costimulatory molecules between both splenic and draining lymph node (DLN) DCs in response to various maturation stimuli. In regards to studies with DLN DCs, it was hypothesized that combinations of CD40 and TLR/adjuvant stimulation that prolong DC persistence and augment maturation status would correlate with enhanced antigen-specific T cell immunity. However, the differences in mature DC phenotype in response to different biological modifiers do not correlate with differences in antigen-specific T cell activation or with differences in tumor immunity. We also examine the cross-talk between CD40 agonist and TLR4 and show that CD40 stimulation of DCs up-regulates TLR4-MD2, the receptor that recognizes lipopolysaccharide (LPS). Overall, our studies highlight how DC biology is regulated both in vitro and in vivo. These findings will be important for DC-based vaccine design as well as our understanding of the DC response to pathogenic and cellular-derived components.
Description	ix, 221 leaves : ill. 28 cm.
Format	application/pdf
Advisor	James D. Gorham.
Subject	Dendritic cells. Biological response modifiers. Immune response -- Regulation. T cells. CD antigens. Dendritic Cells -- Immunology. Receptors
College	Dartmouth Medical School -- Department of Microbiology and Immunology.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.40

Title	Page 1
Format	application/pdf
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Full Text	Regulation of dendritic cell biology in vitro and in vivo with biological response modifiers A Thesis Submitted to the Faculty in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Microbiology and Immunology by Davor Frleta DARTMOUTH COLLEGE Hanover, New Hampshire May 11th, 2004 Examining Committee ____________________________ James D. Gorham, M.D., PhD. (Chairman) ____________________________ Randolph J. Noelle, Ph.D. ____________________________ William F. Wade, Ph.D. ____________________________ Brian L. Kelsall, M.D. ____________________________ Carol Folt, Ph.D. Dean of Graduate Studies

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