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

Monica Vavassori, Rita Maccario, Antonia Moretta, Patrizia Comoli, Andreas Wack, Franco Locatelli, Antonio Lanzavecchia, Emanuela Maserati, Paolo Dellabona, Giulia Casorati, Daniela Montagna

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)5739-5747
Number of pages9
JournalJournal of Immunology
Volume157
Issue number12
Publication statusPublished - Dec 15 1996

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ASJC Scopus subject areas

  • Immunology

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