γδ T cells can be classified through expression of the given γ- and δ -chains of their γδ T cell receptor (TCR) complex and their localization within the body. As innate T lymphocytes they are already at birth highly functional and may immediately protect newborns against pathogenic infections. We assume that extrinsic (self-antigens, microbial exposure) and intrinsic (transcription factors) factors might fine-tune the development, organ-specificity and functional adaptation of murine and human γδ T cells.
Murine IL-17 producing Vγ6 and Vγ4 T cells develop within an embryonic thymus and are maintained as long-living, tissue-resident cells throughout adulthood. In the first part of this project we aim at understanding how the adaptation and maintenance of IL-17 producing γδ T cells is regulated through underlying transcriptional mechanisms. We will apply single-cell RNA sequencing (single-cell RNA-seq) technologies and bioinformatics to analyze and compare the heterogeneity and transcriptional differences of tissue-specific IL-17 producing γδ T cells.
In the second part of this project we characterize the functional adaptation of human γδ T cells in neonates and adults. We and other could recently show by next generation sequencing of human γδ TCRs that adult, but not neonatal, γδ TCR repertoires display a high diversity and consist of individual, expanded γδ T cell clones. We hypothesize that innate γδ T cells are a first set of standard effector cells and are only present in early childhood. Now we aim at understanding how the expansion of individual γδ T cell clones throughout life is reflected and controlled through gene expression and epigenetic programs.
