Human virus-specific T cells in peripheral blood and lymph nodes: Phenotype, function and clonal relationships

The research presented in this thesis focusses on the characterization of the T cell response against (persistent) viral infections. We have studied the clonal evolution of peripheral blood and lymph node derived virus-specific CD8+ and CD4+ T cells during both primary infections and reactivations. We have analysed the impact of the tissue (lymph node) on the phenotype and function of virus-specific CD8+ T cells. We also examined the relationship between transcription factor expression, phenotype and the functional profile of virus-specific CD8+ T cells.
The combination of multifluorochrome flowcytometry and next generation sequencing used in this thesis shows that it is possible to characterize many aspects of the human anti-viral immune response.
Thus, this thesis paves the way for a better understanding of the phenotype, function and clonal relationships of virus-specific CD4+ and CD8+ T cells directed against many more proteins derived from many more viruses in a wide variety of tissues. The fact that an ever smaller sample can be used to perform such an analysis without loss of information, will allow for the study of virus-specific CD4+ and CD8+ T cells with extremely low frequencies and the analysis of anti-viral responses in small samples such as biopsies.