Role of T-cells in peritoneal dialysis related inflammation

Roberts, Gareth Wyn 2008. Role of T-cells in peritoneal dialysis related inflammation. PhD Thesis, Cardiff University.

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Abstract

Despite advances in treatment, peritoneal infection remains one of the main causes of technique failure in Peritoneal Dialysis (PD) patients. Understanding the nature of the peritoneum's response to inflammation is vital if we wish to reduce the negative impact of inflammation and infection on the peritoneal membrane. Given that aberrant leukocyte recruitment and activation appears to be a feature of these responses it is particularly important that we understand the contributions made by both resident and recruited peritoneal leukocytes in controlling this process as well as their direct contribution to membrane damaging events. Data presented in this thesis has shown that the peritoneal T-cell pool is a heterogeneous mixture of specialized T-cell subsets. In contrast to previous observations, we have shown that (under appropriate conditions) these cells are capable of being activated, though their effector function appears to be tightly regulated by peritoneal dendritic cells. The phenotype and activation threshold of peritoneal T-cells differs markedly from that of peripheral blood T-cells in that the peritoneal cavity is enriched in both effector memory and regulatory T-cells. These cells exist in a delicate equilibrium to both maintain homeostasis and ensure prompt removal of invading pathogens. During episodes of acute inflammation (peritonitis) further specialized T-cell subsets (TH17 and Vy9S2 T- cells) are recruited into the peritoneal cavity. These cells form part of the early immune response and are a pivotal link between the innate and adaptive arms of the immune response. Recurrent peritonitis has a detrimental impact on the function of peritoneal T- cells, impairing both the proliferation and effector function of these cells. This peritoneal T-cell dysfunction contributes to a state of immuno-suppression thus potentially rendering the patients more susceptible to further episodes of peritonitis. It is also likely to have a negative impact on immuno-resolution and contribute to neutrophil retention, chronic inflammation and membrane fibrosis.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
ISBN:	9781303184697
Date of First Compliant Deposit:	30 March 2016
Last Modified:	10 Jan 2018 04:55
URI:	https://orca.cardiff.ac.uk/id/eprint/55774

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