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Titel: Expression of CD38, CD226, CD39, PD1 on T cells in chronichepatitis B and their correlation with serum vitamin D levels
Sonstige Titel: Expression von CD38, CD226, CD39, PD1 in den T-Zellen chronischer Hepatitis B Patienten und ihre Korrelation mit dem Vitamin D Spiegel im Serum
Sprache: Deutsch
Autor*in: Bai, Pingping
GND-Schlagwörter: Immunologie
Erscheinungsdatum: 2014
Tag der mündlichen Prüfung: 2015-02-12
Zusammenfassung: 
To analyze the profile of peripheral blood T lymphocyte subpopulations and serum vitamin D levels in chronic hepatitis B patients, 45 out-patients with CHB (treatment naïve, n=28; under treatment, n=17) 18 healthy individuals were selected aimed at comprehensive analyzing the peripheral blood T lymphocyte subpopulation profile in CHB patients, and to assess their function by measuring their expression of activation/exhaustion markers (CD38, HLA-DR, CD226, CD39/CTLA4, PD1) using flow cytometry. Further investigated serum vitamin D levels and its correlation with the expression of activation/exhaustion markers on T cells in chronic HBV infection.
Among all the costimulatory and coinhibitory markers, we demonstrated an increased expression of PD1 on Tregs in CHB cohort, which is also positively correlated with HBV DNA replication, emphasized the important role of Tregs in persistance of HBV infection. Meanwhile, a reduction of costimulatory molecule, CD39, expression on effectory memory CD8 T cells suggested the balance between costimulatory and coinhibitory molecules is broken in CHB. A significant increase in CD226 levels on CD4 nonTreg cells and CD8 T cells and its CD45RA + subsets (CD8N and CD8TerEM) in CHBt group compared to healthy controls, suggested that CD226 might be a marker implies that the immune response start to restore. The increased frequencies of CD38 on CD8 T cells and Treg subsets concomitant with elevated HBV DNA replications in CHBn patients, consistent with the results of previous studies, emphasized that CD38 is a marker of sustained viral replication in CHB. Moreover, we demonstrated a prevalence of vitamin D insufficiency in CHB patients, but no correlation between HBV viral loads and 25(OH)D serum levels, as well as ALT serum levels. Therefore, we consider that there is no direct correlations between 25(OH)D serum levels and HBV viral replication, intrahepatic inflammation. However, our study displayed a reverse correlation between 25(OH)D serum levels and frequency of CD8 T cells, proportion of CD226+ CD8CM, and a positive correlation between 25(OH)D serum levels and frequency of CD8N T cells, the expression of PD1 on CD8PreEM in peripheral blood in CHBn group.
Whereas, within Tregs, only negative correlation between 25(OH)D serum levels and proportion of HLADR+ rTregs was found. This may demonstrated that, in CHB vitamin D suppresses the activation of CD8 T cells more than increases Tregs, suggests at least vitamin D may perform an unique immunomodulatory function at the pressure of HBV.
For these conclusion, more studies in vivo are needed to investigate the replication of HBV DNA and T cell response incubated with vitamin D and its metabolites, in order to provide a theoretical basis for clinical studies of vitamin D application as a complementary therapy.
Meanwhile, attention should also be placed in innate immune response in CHB, while vitamin D may protect infected hepatocytes from cytotoxic T cell induced cell death, whereas enhence the innate immunity to control virus.
URL: https://ediss.sub.uni-hamburg.de/handle/ediss/5791
URN: urn:nbn:de:gbv:18-72213
Dokumenttyp: Dissertation
Betreuer*in: Lüth, Stefan (PD Dr.)
Enthalten in den Sammlungen:Elektronische Dissertationen und Habilitationen

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