Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

The Regulation of Dendritic Cell Function in Autoimmune Prone and Wild Type Mice

Flores, Rafael R. (2005) The Regulation of Dendritic Cell Function in Autoimmune Prone and Wild Type Mice. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

Primary Text

Download (3MB) | Preview


Dendritic cells (DCs) represent a heterogeneous set of antigen presenting cells linking the innate and adaptive immune systems. DCs are referred to as professional antigen presenting cells (APCs) with regards to their ability to activate naïve T cells. In this study, the role that DCs play in the pathogenesis of Type 1 Diabetes (T1D) was initially examined. We utilized an experimental model that allowed for the generation of bone marrow derived-dendritic cells (BM-DC) subsets that exhibit either a DC type 1 (DC1) or DC2 phenotype. We define DC1 as cells capable of producing high levels of IL-12 and inducing naïve CD4+ T cell differentiation into T helper 1 (Th1) cells while DC2 are cells that produce low levels of IL-12 and induce Th2 cell differentiation. During the course of this study we also utilized several toll-like receptor (TLR) ligands to activate DC function. In addition, we tracked the migration of DCs in vivo utilizing a novel perfluoropolyether (PFPE) contrasting agent in conjunction with a modified magnetic resonance imaging (MRI) instrument. With this methodology we tested the hypothesis that NOD DCs were predisposed to adopt a DC1 phenotype that contributed to the pathogenesis of T1D. The results from our experiments show that NOD BM-DCs induced into a DC1 or DC2 functional phenotype exhibit no significant intrinsic differences in their production of IL-10 or IL-12, in comparison to wild type mice. Additionally, NOD BM-DCs expressed similar levels of CD80, CD86, CD40, and MHC class II in comparison to wild type BM-DC. Our analysis did show that the production by BM-DCs of IL-10, induced by CpG ODN, is negatively regulated by IFN-gamma. The suppressed production of IL-10 may have implications for the development of T helper cell type 1 (Th1) and Th2 cells. Altogether our study has shown that, 1) NOD BM-DCs are not intrinsically skewed towards a DC1 phenotype, 2) IFN-gamma negatively regulates the production of IL-10 in BM-DCs, and 3) NOD BM-DCs can be successfully imaged in vivo using a novel PFPE labeling/MRI detection technique.


Social Networking:
Share |


Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Flores, Rafael R.rrfst6@pitt.eduRRFST6
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMorel, Penelope A.morel@pitt.eduMOREL
Committee MemberAhrens, Eric
Committee MemberKalinski, Pawelpak5@pitt.eduPAK5
Committee MemberPlevy, Scott
Committee MemberRidgway, William
Date: 25 July 2005
Date Type: Completion
Defense Date: 20 May 2005
Approval Date: 25 July 2005
Submission Date: 28 June 2005
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Immunology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: dendritic cells; IFN-gamma; IL-10; IL-12; nonobese diabetic mice; type 1 diabetes
Other ID:, etd-06282005-180939
Date Deposited: 10 Nov 2011 19:48
Last Modified: 15 Nov 2016 13:45


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item