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Role of the CTLA-4 receptor in regulatory T cell development, homeostasis and function

Schmidt, Emily Marta (2010)
Ph.D. thesis, University of Birmingham.

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Abstract

Autoimmunity can occur when self-reactive lymphocytes of the adaptive immune system are activated upon encounter with antigen. This can lead to the development of debilitating and potentially life-threatening autoimmune diseases such as type-1 diabetes, rheumatoid arthritis and multiple sclerosis. Regulatory T cells (Tregs) are a subset of CD4+ T cells that express the lineage-specific transcription factor Foxp3 and exert dominant peripheral tolerance to maintain immune homeostasis. It is therefore important to fully understand the underlying mechanisms of Treg development, homeostasis and function due to the positive and negative effects that therapeutic manipulation could have on this essential T lymphocyte population. Many effector molecules have been proposed to have a central role in regulatory T cell function, and it is now clear that Tregs are equipped with multiple mechanisms by which to exert suppressive function. It has been reported that the cytotoxic T lymphocyte antigen-4 (CTLA-4) receptor is constitutively expressed by regulatory T cells and a role for this molecule in Treg suppression has been suggested. This investigation revealed a role for CTLA-4 in maintaining homeostasis of the peripheral regulatory T cell compartment. In addition, using a transgenic mouse model that permitted the development of antigen-specific Ctla-4-deficient Tregs, a role for the CTLA-4 receptor in Treg suppressive function was identified. The data obtained suggest that the CTLA-4 receptor may function on regulatory T cells by modulating CD80/CD86 co-stimulatory molecule expression by antigen-presenting cells, and hence their capacity to activate conventional T cells to generate effector T cells and instigate an effective immune response.

Type of Work:Ph.D. thesis.
Supervisor(s):Walker, Lucy
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Immunology, Infection and Inflammation
Subjects:QR180 Immunology
Institution:University of Birmingham
Library Catalogue:Check for printed version of this thesis
ID Code:1291
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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