Large-scale generation of human allodepleted anti-3rd party lymphocytes.
Although adoptive transfer of donor lymphocytes protects from infections and relapse after allogeneic hematopoietic stem cell transplantation in both mice and in men, it is associated with a high risk of graft versus host disease (GvHD) which rises with HLA mismatching and the number of T lymphocytes that are infused. Elimination/reduction of alloreactive donor T lymphocytes is an appealing approach and several strategies have been proposed. Here we describe generation of anti-3rd party T lymphocytes under conditions of IL-2 deprivation and their effects in a pre-clinical murine model. Our results clearly indicated that anti-3rd party T lymphocytes generated on a large scale by means of IL-2 deprivation maintain a broad T cell repertoire, do not proliferate in a mixed lymphocyte reaction and do not cause GvHD in NOD-SCID mice. These anti-3rd party lymphocytes contain a large adaptive T regulatory cell subset which might contribute to in vitro and in vivo immune modulation.
De Ioanni
Maria
M
Department of Clinical and Experimental Medicine, IRCCS Foundation on Transplantation Biotechnologies, University of Perugia, Italy.
Di Ianni
Mauro
M
Bonifacio
Elisabetta
E
Moretti
Lorenzo
L
Cecchini
Debora
D
Bazzucchi
Federico
F
Terenzi
Adelmo
A
Aloisi
Teresa
T
Falzetti
Franca
F
Aversa
Franco
F
Reisner
Yair
Y
Martelli
Massimo F
MF
Tabilio
Antonio
A
D000818:Animals; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D006086:Graft vs Host Disease / Q000517:prevention & control; D007376:Interleukin-2 / Q000172:deficiency / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion / Q000379:methods*; D017710:Lymphocyte Transfusion / Q000379:methods*; D051379:Mice; D023421:Models, Animal; D015996:Survival Rate; D013601:T-Lymphocytes / Q000166:cytology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology
D007376:Interleukin-2