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Evidence of a thymic abnormality in relapsing-remitting multiple sclerosis

The peripheral naive CD4 T cell pool is homeostatically regulated through a balance of thymic production, delivery of survival signals and homeostatic proliferation. CD4 recent thymic emigrants (RTEs) have a high T cell receptor excision circle (TREC) content and express high levels of CD31. We report premature thymic involution in RRMS, initiated by reduced numbers of naive CD4 T cells and various naive CD4 T cell subsets in peripheral blood. Further, CXCR4, a receptor involved in emigration from the thymus, and CD127 and Bcl-2 (survival signals) are upregulated in various naive CD4 T cell subsets in RRMS. As a compensatory process, naive CD4 T cells undergo homeostatic proliferation. This proliferation is a form of peripheral positive selection through self-MHC/self-antigen interaction and thus can contribute to the expansion of autoreactive T cells and predispose to development of RRMS.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.111617
Date January 2008
CreatorsWilliams, Julia Leigh.
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageMaster of Science (Department of Pathology.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 003135256, proquestno: AAIMR66720, Theses scanned by UMI/ProQuest.

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