Donor T Cell Repertoire Profiling in Recipient Lymphoid and Parenchyma Organs Reveals GVHD pathogenesis at Clonal Levels after Bone Marrow Transplantation in mice

The success of allogeneic hematopoietic cell transplantation (allo-HCT) is undermined by the development of graft-versus-host disease (GVHD). Using next-generation sequencing of TCRbeta chain locus, we defined the feature of T-cell repertoires in mice after syngeneic or allogeneic bone marrow transplantation. We extensively studied post-transplant T-cell repertoire in multiple lymphoid and non-lymphoid GVHD target organs, including peripheral blood, spleen, peripheral lymph nodes, mesenteric lymph nodes, liver, lungs, gut and skin. Our study provides a spectrum analysis of T-cell repertoire recovery across broad tissue sites. We examined the potential of blood sample as tool to predict the dominant clones in GVHD target organs and detection of de novo generated top clones from pre-transplant donor T cells. Our study highlights the importance of T-cell repertoire profiling in understanding the biology of allogeneic T-cell response and immune repertoire sequencing-based methods may represent a novel personalized strategy to guide diagnosis and therapy in GVHD.