TY - JOUR
T1 - Restricted TCR Repertoire and Long-Term Persistence of Donor-Derived Antigen-Experienced CD4+ T Cells in Allogeneic Bone Marrow Transplantation Recipients
AU - Vavassori, Monica
AU - Maccario, Rita
AU - Moretta, Antonia
AU - Comoli, Patrizia
AU - Wack, Andreas
AU - Locatelli, Franco
AU - Lanzavecchia, Antonio
AU - Maserati, Emanuela
AU - Dellabona, Paolo
AU - Casorati, Giulia
AU - Montagna, Daniela
PY - 1996/12/15
Y1 - 1996/12/15
N2 - 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.
AB - 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.
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M3 - Article
C2 - 8955228
AN - SCOPUS:0030589363
VL - 157
SP - 5739
EP - 5747
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -