The role of sialoadhesin in the pathogenesis of autoimmune eye inflammation

Description

This thesis aimed to determine whether Sn expression did not occur on cells other than macrophages and how Sn expression influenced T cell responses responsible for autoimmunity using the EAU mouse model of human ocular inflammation, uveitis.  Sn’s effects were studied on the C57BL/6 genetic background using mice of Sn⁺/⁺ and Sn^-/- genotype.  Mice confirmed to have Sn⁺/⁺ and Sn^-/- genotype and phenotype were immunised with IRBP-20 peptide in adjuvant to induce EAU.  The effects of Sn deletion on EAU were analysed by studying subsequent Thl immune responses and their effects on EAU disease progression. Flow cytometry analysis of the draining lymph nodes (dLN) and spleens of naïve mice identified Sn-expressing cells with phenotype consistent with conventional dendritic cells (DCs) of myeloid and lymphoid types.  These cells expressed DEC205⁺CD8αα-and DEC205⁺CD8αα⁺ phenotype, respectively.  CD8αα⁺ cells were considered to be of lymphoid type rather than plasmacytoid because they expressed CD8αα⁺ at levels similar to T cells and high levels of DEC205 which are typical feature of lymphoid DCs.  DEC205⁺CD8αα^- cells were considered to be myeloid-derived because of their expression of macrophage-like phenotype and DEC205.  DEC205⁺CD8αα^- cells maintained high levels of Sn expression when purified.  They could be propagated in vitro using conditions typical for CD14-derived DCs to yield Sn-expressing cells with allogeneic leukocyte stimulatory capacity that was higher than macrophages which was consistent DCs of this type.  The basal levels of Sn on the two DCs subtypes in naive mice were upregulated in response to immunisation.  Sn upregulation strongly correlated with elevated levels of MHC II and B7.2 expression on the CD11c⁺DEC205⁺CD8αα^- and CD11c⁺DEC205⁺CD8αα⁺ cells.  These changes coincided with the highest level of T cell proliferative responses in immunised Sn⁺/⁺ and Sn^-/^- mice that occurred 6 days post-immunisation.  Supporting the existence of Sn-expressing DCs was the presence of a small subset of Sn⁺ cells with DC morphology that co-expressed MHC II and CD11c in EAU inflammatory lesions.  However, these Sn⁺MHC II⁺ cells comprised a very minor proportion of the total MHC II⁺ cells in the diseased eye.  Thus in addition to macrophages, Sn is also expressed on CD11c⁺DEC205⁺ conventional DCs of myeloid (CD11b⁺CD8αα^-) and lymphoid (CD11b^-CD8αα⁺) type in the dLN, the spleen and the eye and its expression increases following immunisation.

Links & Downloads

1. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.439950

Tags

617.71

Additional Fields

Identifer	oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:439950
Date	January 2006
Creators	Hwenda, Lenias
Publisher	University of Aberdeen
Source Sets	Ethos UK
Detected Language	English
Type	Electronic Thesis or Dissertation