Human gamma delta T cells are quickly reconstituted after stem-cell transplantation and show adaptive clonal expansion in response to viral infection

To investigate how the human gamma delta T cell pool is shaped during ontogeny and how it is regenerated after transplantation of hematopoietic stem cells (HSCs), we applied an RNA-based next-generation sequencing approach to monitor the dynamics of the repertoires of gamma delta T cell antigen receptors (TCRs) before and after transplantation in a prospective cohort study. We found that repertoires of rearranged genes encoding gamma delta TCRs (TRG and TRD) in the peripheral blood of healthy adults were stable over time. Although a large fraction of human TRG repertoires consisted of public sequences, the TRD repertoires were private. In patients undergoing HSC transplantation, gamma delta T cells were quickly reconstituted; however, they had profoundly altered TCR repertoires. Notably, the clonal proliferation of individual virus-reactive gamma delta TCR sequences in patients with reactivation of cytomegalovirus revealed strong evidence for adaptive anti-viral gamma delta T cell immune responses.