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.

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

MASERATI, EMANUELA;
1996

Abstract

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.
Vavassori, M.; Maccario, R.; Moretta, A.; Comoli, P.; Wack, A.; Locatelli, F.; Lanzavecchia, A.; Maserati, Emanuela; Dellabona, P.; Casorati, G.; Montagna, D.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11383/6697
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