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CD161+ T cells in Immune Regulation

Duurland, CL; (2017) CD161+ T cells in Immune Regulation. Doctoral thesis , UCL (University College London).

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Final PhD thesis Chantal Duurland-28022017.pdf
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Abstract

Immune regulation is an important process in the human body to maintain immune homeostasis. Regulatory T cells (Treg) are important in this process, however, under specific conditions, Treg can produce pro-inflammatory cytokines. These cytokine-producing Treg are identified by expression of CD161, a C-type lectin receptor expressed by Th17 cells. Both CD161+ Treg and CD161+ conventional T cells (Tconv) are enriched at the inflamed site in childhood arthritis indicating that these cells might be involved in disease pathogenesis. Therefore, the aim of this thesis is to understand the role of CD161+ T cells in immune regulation. Analysis of transcriptional and protein signatures of CD161+ Treg compared to CD161- Treg, and CD161+ Tconv compared to CD161- Tconv from blood of healthy adults identified a shared signature between CD161+ Treg and CD161+ Tconv. CD161+ Treg express similar or higher levels of markers associated with a Treg phenotype. In addition, both CD161+ Tconv and CD161+ Treg express high levels of markers associated with Th1 and Th17 cells, and tissue homing including receptors for gut homing, which are upregulated in response to retinoic acid. Despite the shared signatures of CD161+ Tconv and CD161+ Treg, their TCRβ repertoire is largely non-overlapping. CD161+ Tconv and CD161+ Treg from synovial fluid (SF) also produce pro-inflammatory cytokines, express markers associated with Th1 and Th17 cells, and are suppressive in an in vitro suppression assay. Expression of gut homing receptors by CD161+ T cells was lower in SF compared to blood. Analysis of TCRβ repertoire of CD161+ and CD161- Tconv, and CD161+ and CD161- Treg from SF revealed overlap between CD161+ and CD161- T cell populations, and CD161+ Tconv and CD161+ Treg. The data presented in this thesis highlights a potential role for CD161+ T cells in disease pathogenesis and suggest that CD161 expression is regulated differently in health and disease.

Type: Thesis (Doctoral)
Title: CD161+ T cells in Immune Regulation
Event: University College London
Language: English
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
URI: http://discovery.ucl.ac.uk/id/eprint/1543089
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