RESTRICTED TCR REPERTOIRE AND LONG-TERM PERSISTENCE OF DONOR-DERIVED ANTIGEN-EXPERIENCED CD4(-CELLS IN ALLOGENEIC BONE-MARROW TRANSPLANTATION RECIPIENTS() T)

We investigated the contribution of transfer of Ag-experienced donor T cells to the immune reconstitution of allogeneic bone marrow transpla ntation (BMT) recipients. To this purpose, we used a combination of ce ll culture methods to isolate tetanus toroid (TT)-specific T cell clon es, and a sensitive and specific heteroduplex analysis to monitor the presence of a particular clonotype using TCR N region sequences. We do cument that patients after BMT display a small response to TT, entirel y accounted for by few donor-derived clones. These patients show a str ong polyclonal response to TT vaccination; however, the T cell clones transferred with the transplant can still be detected within the polyc lonal T cell lines for up to at least 5 yr after BMT. We also demonstr ate that vaccination of donors with TT before BMT results in a more re levant 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 adopti ve transfer of protective T cell immunity into recipients, and suggest the possibility of using preventive T cell adoptive therapy in conjun ction with marrow infusion.