Interest of T cell adoptive transfer after bone marrow transplantation

Intensive treatments preceding the injection of hematopoietic stem cells have a dual effect on the T system by destroying most peripheral T lymphocytes, together with the essential part of the patient's immunological memory, and altering the anatomical regions conducive to their differentiation. In the case of allogeneic grafts, these effects are worsened by the immunosuppressive treatments administred to prevent graft-versus-host disease (GVHD) as well as by GVHD itself, if it occurs. Deprived of his immunological memory as well as part of his capacity to create a new T cell repertoire rapidly, the patient is exposed to infectious and tumoral risks during an indefinite regenerative period. However, mature T lymphocytes are also provided with the graft in a highly variable amount depending on the graft conditions chosen. These T lymphocytes are potential carriers of antiviral and antitumoral specificities but also of allogeneic specificities directed against the recipient. The latter have antinomic action since they are responsible both for GVH reaction and the anti-leukemic effect (GVL). The benefit of adoptive transfer of specific T lymphocytes is thus obvious, and the conditions for its implementation and success are rather easy to determine in order to restore antiviral immunity. In contrast, successful induction of specific antitumoral activity requires that the causes of initial failure be recognized first, wether quantitative or qualitative. Finally, it is now possible to envisage the production of a controlled allogeneic reaction and to search for conditions in which an antileukemic effect could occur without endangering the life of the patient in the event of GVH reaction. This review considers the reasons and the current possibilities, after grafts of hemopoietic stem cells, for using adoptive transfer of T cells directed against tumor cells (by targeting tumoral or allogeneic antigens) or viruses (e.g. Epstein-Barr virus or cytomegalovirus).