Einfluss von Alter und HLA-Haplotyp auf das TCR-VB-Repertoire und Lymphozyten Subtypen im peripheren Blut.

Diese Arbeit befasste sich mit flusszytometrischen Analysen von peripherem Blut gesunder Probanden. Entzündliche-, Autoimmun-, oder Tumorerkrankungen verän-dern das TCR-VB-Repertoire von gesunden Menschen. Um diese Veränderungen untersuchen zu können, muss man die Normalverteilung des TCR-VB-Reperto...

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Bibliographic Details
Main Author: Gaber, Rami
Contributors: Hemmer, Bernhard (Prof.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2009
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This study focused on flowcytometric analysis of peripheral blood of healthy donors. The TCR-VB-repertoire of healthy test persons is changed by inflammatory-, auto-immune- and tumour diseases. One has to know about the normal distribution of the TCR-VB-repertoire in order to explore these changes. Besides the above mentioned diseases, only little is known about factors influencing lymphocytes and the TCR-VB-repertoire in the peripheral blood. Age is a factor of importance as form and function of the T-lymphocytes are changed permanently after contact with antigens. HLA plays a decisive role in the T-cell maturation through the positive and negative selection in the thymus and thus in the development of the TCR-VB-repertoire. In our population we found that the TCR-VB-repertoire was very homogeneous. Thus our data can be used as reference values for research on changes due to inflammatory- or autoimmune diseases as well as for clinical monitoring of the T-cell population in therapies. The fact that humans with different HLA-haplotypes have a very homogenous TCR-VB-repertoire implies that the influence of HLA on the developing TCR-VB-repertoire is less important than germline-factors. Nevertheless for some HLA types the data showed significant differences in the expression of single TCR-VB-chains in comparison to test persons without the HLA type. These differences were even more distinct when comparing donors with homozygous alleles to donors with heterozy-gous alleles and donors without these alleles. The expression of single TCR-VB-chains is constant in the course of life-time with an increasing number of expanded chains in the elderly. Those chains are clonal ex-pansions of T-cells that were developed during the course of life through infections. We didn’t find any significant changes in B-cells and natural killer cells during the course of life-time.