Restricted TCR Repertoire and Long-Term Persistence of Donor-Derived Antigen-Experienced CD4+ T Cells in Allogeneic Bone Marrow Transplantation Recipients

We investigated the contribution of transfer of Ag-experienced donor T cells to the immune reconstitution of allogeneic bone marrow transplantation (BMT) recipients. To this purpose, we used a combination of cell culture methods to isolate tetanus toxoid (TT)-specific T cell clones, and a sensitive and specific heteroduplex analysis to monitor the presence of a particular clonotype using TCR N region sequences. We document that patients after BMT display a small response to TT, entirely accounted for by few donor-derived clones. These patients show a strong polyclonal response to TT vaccination; however, the T cell clones transferred with the transplant can still be detected within the polyclonal T cell lines for up to at least 5 yr after BMT. We also demonstrate that vaccination of donors with TT before BMT results in a more relevant transfer of Ag-experienced T cells, allowing the recipients to mount a strong polyclonal response without need of vaccination. These findings provide a rationale for vaccinating donors to optimize adoptive transfer of protective T cell immunity into recipients, and suggest the possibility of using preventive T cell adoptive therapy in conjunction with marrow infusion.