Revisiting The Role Of Gamma Delta T Cells In Anti-Cmv Immune Response After Transplantation

Gamma delta (gamma delta) T cells form an unconventional subset of T lymphocytes that express a T cell receptor (TCR) consisting of gamma and delta chains. Unlike conventional alpha beta T cells, gamma delta T cells share the immune signature of both the innate and the adaptive immunity. These features allow gamma delta T cells to act in front-line defense against infections and tumors, rendering them an attractive target for immunotherapy. The role of gamma delta T cells in the immune response to cytomegalovirus (CMV) has been the focus of intense research for several years, particularly in the context of transplantation, as CMV reactivation remains a major cause of transplant-related morbidity and mortality. Therefore, a better understanding of the mechanisms that underlie CMV immune responses could enable the design of novel gamma delta T cell-based therapeutic approaches. In this regard, the advent of next-generation sequencing (NGS) and single-cell TCR sequencing have allowed in-depth characterization of CMV-induced TCR repertoire changes. In this review, we try to shed light on recent findings addressing the adaptive role of gamma delta T cells in CMV immunosurveillance and revisit CMV-induced TCR reshaping in the era of NGS. Finally, we will demonstrate the favorable and unfavorable effects of CMV reactive gamma delta T cells post-transplantation.