Hepatic haematopoietic stem cells and the T Cell development potential of the adult human liver
Citation:
Lucy Golden-Mason, 'Hepatic haematopoietic stem cells and the T Cell development potential of the adult human liver', [thesis], Trinity College (Dublin, Ireland). Department of Immunology, 2002, pp 311Download Item:
Golden Mason TCD THESIS 6792 Hepatic haematopoietic.pdf (PDF) 168.6Mb
Abstract:
Large populations of innate T cells are found in the normal adult human liver (AHL), some of which may differentiate locally. The AHL also contains populations of functional myeloid and erythroid progenitors. The co-expression of lineage-specific markers on hepatic haematopoietic progenitors has not been examined. In this study, the presence and phenotype of lineage- committed haematopoietic progenitors in the normal AHL was investigated and compared to the profiles of differentiating haematopoietic precursor populations detected in liver bearing metastases of colonic origin. Levels of haematopoietic stem cells (HSCs, CD34+CD45+) were increased six fold when compared to matched peripheral blood samples. In normal liver, less than 5% of HSCs expressed the myeloid associated antigen CD33 whereas considerable proportions expressed lymphoid associated markers (T cell 33.39%, B cell 17.39% and natural killer cell 37.17%). Significant increases were observed in the relative proportions of hepatic HSCs co-expressing CD33 (20.53%, p = 0.001), and the T cell associated antigen CD7 (58.13%, p = 0.02) in tumour-bearing liver compared to normal liver. HSCs with B-cell progenitor phenotype (CD19+) were significantly decreased in tumour-bearing liver (0.06%, p = 0.02). Despite these differences, the activation status of haematopoiesis, as measured by the co-expression of the differentiation and activation markers (CD38 and CD45RA), did not differ significantly between normal and tumour-bearing liver. Using confocal microscopy, HSCs were localised to portal tract areas in normal hepatic tissue. These results indicate that the normal adult human liver harbours lineage committed haematopoietic progenitors and the vast majority of these progenitors express lymphoid associated antigens with changes occurring in both the myeloid and lymphoid compartments of the hepatic haematopoietic pathway on tumour challenge.
Author: Golden-Mason, Lucy
Advisor:
O'Farrelly, ClionaQualification name:
Doctor of Philosophy (Ph.D.)Publisher:
Trinity College (Dublin, Ireland). Department of ImmunologyNote:
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Immunology, Ph.D., Ph.D. Trinity College DublinLicences: