Investigating the regulatory cells that mediate recovery from CNS-targeted autoimmune disease
Year: 2004
Type: dissertation
Abstract: Autoimmune disease, such as multiple sclerosis, results from the breakdown of immune tolerance to self.The goal of therapy is to restore this state of tolerance, and understanding how this may occur physiologically is important for improving intervention strategies.Experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis in which disease is induced by immunisation with antigenic components of myelin.In B6 mice, disease course is monophasic and mice spontaneously enter remission, providing an ideal scenario to study the natural restoration of tolerance.IL-10-deficient mice fail to recover from EAE, and it is thought that production of IL-10 within the CNS is particularly important for recovery.Previous work from the Anderton lab had also shown B cell production of the immunoregulatory cytokine IL-10 to be vital for recovery.The aim of this PhD was to further investigate the role of IL-10 producing B cells and CD4 T cells during remission from EAE.While B cells clearly play an important role in recovery, and post-recovery B cells can transfer protection to naïve recipients, B cells do not localise to the CNS.Instead, IL-10 producing CD4 cells having phenotypic markers and functional characteristics of regulatory T cells were found to accumulate in the CNS during recovery.Depletion of CD25 cells in vivo resulted in impaired recovery, and transfer of CD4 + CD25 + cells from recovering mice protected recipients, further confirming a role for these cells.Thus, regulation through IL-10 production appears to be mediated by both B cells and CD4CD25 T cells in this model.5.2.12.Transfer of low numbers of CD4CD25 cells from recovering mice protects naïve recipients against EAE induction 5.2.13.Depletion of CD25 cells after recovery restores susceptibility to reinduction ofEAE 141 5.3.DISCUSSION: 6.DISCUSSION 6.1.Regulation ofTcell mediated CNS-targeted autoimmuie disease by IL-JO 6.2.Questions remaining 6.2.1.What is the mechanism of suppression by CD4CD25 cells in this model?6.2.2.What is the Ag-reactivity of the IL-10 producing B cells and CD4CD25 cells, and how are they expanded in vivo?6.2.3.Is there a relationship between regulatory T cells and B cells 6.3.Therapeutic potential of regulatory T cells.6.3.1.Ex vivo expansion of Tregs 6.3.2.Non-antigen-specific expansion of Tregs in vivo 6.3.3.Ag-specific Induction/Expansion of Tregs in vivo 6.4.Conclusions 7.
Source: ERA
Author: Mandy J. McGeachy
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2341719916