1. Large-scale generation of human allodepleted anti-3rd party lymphocytes.
- Author
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De Ioanni M, Di Ianni M, Bonifacio E, Moretti L, Cecchini D, Bazzucchi F, Terenzi A, Aloisi T, Falzetti F, Aversa F, Reisner Y, Martelli MF, and Tabilio A
- Subjects
- Animals, Cell Culture Techniques, Graft vs Host Disease prevention & control, Interleukin-2 deficiency, Interleukin-2 pharmacology, Lymphocyte Culture Test, Mixed, Mice, Models, Animal, Survival Rate, T-Lymphocytes, Regulatory cytology, Cell Proliferation, Lymphocyte Depletion methods, Lymphocyte Transfusion methods, T-Lymphocytes cytology
- Abstract
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.
- Published
- 2008
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