Show simple item record

dc.contributor.authorKishore, Madhav
dc.identifier.citationKishore, M. 2016, The role of co-stimulatory receptors in the regulation of regulatory T cell migration. Queen Mary University of London.en_US
dc.descriptionMD (res)en_US
dc.description.abstractOnce an immune response is initiated, a combination of several mechanisms coordinates and directs the homing of T cells to their target tissue. Co-stimulatory receptors expressed on the surface of T lymphocytes are known to actively regulate T cell motility and thus are crucial for regulating T cell migration. The B7 co-stimulatory receptor family members CD28 and CTLA-4 are well known to positively and negatively regulate effector T cell motility respectively. However, their effect on motility and subsequently migration has not been specifically studied in regulatory T cells (Tregs). Tregs are a CD4+ T cell subset fundamental for maintaining immune homeostasis and their role in controlling autoimmunity has been well established through a variety of experimental animal models. Tregs differ from conventional T cells in their expression of CTLA-4. While conventional T cells express CTLA-4 only after activation, Tregs are known to express this negative co-stimulatory receptor constitutively. Additionally, Tregs display a distinct metabolic phenotype to that of conventional T cells. This thesis examines the impact of both co-stimulatory receptors on Treg migration while taking in account the consequences of the concomitant delivery of signals from both. The data in this study suggests that glycolysis, rather than lipid oxidation induced by CD28 promotes Treg migration through glycolytic enzymes including glucokinase, whose expression in T cells was previously unknown. In contrast, CTLA-4 inhibits CD28 induced Treg migration via inhibition of these glycolytic enzymes. The therapeutic implications of these results in the context of disease and transplantation are discussed. CD31, an IgG like molecule, is expressed on a number of leukocytes including lymphocytes. In T cells, CD31 inhibits activation by recruiting phosphatases through its cytoplasmic ITIM domains and has thus been described as a co-inhibitory receptor. The role of this co-receptor in the regulation of T cell migration is investigated in the last part of this thesis. Our observations suggest that CD31 selectively signals in activated T cells to regulate their migration in response to inflammatory chemokines, revealing an additional role of this receptor in regulating T cell-mediated inflammation
dc.publisherQueen Mary University of Londonen_US
dc.subjectregulatory T cellsen_US
dc.subjectT cell migrationen_US
dc.titleThe role of co-stimulatory receptors in the regulation of regulatory T cell migration.en_US
dc.rights.holderThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author

Files in this item


This item appears in the following Collection(s)

  • Theses [3068]
    Theses Awarded by Queen Mary University of London

Show simple item record