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.
Vavassori
M
M
Unit of Immunochemistry, DIBIT, H.S. Raffaele Scientific Institute, Milan, Italy.
Maccario
R
R
Moretta
A
A
Comoli
P
P
Wack
A
A
Locatelli
F
F
Lanzavecchia
A
A
Maserati
E
E
Dellabona
P
P
Casorati
G
G
Montagna
D
D
D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002470:Cell Survival; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D008213:Lymphocyte Activation; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013745:Tetanus Toxoid / Q000276:immunology; D014611:Vaccination
D016693:Receptors, Antigen, T-Cell, alpha-beta; D013745:Tetanus Toxoid