IL-7 induced immune reconstitution after bone marrow transplantation and enhanced graft vs. leukemia effect

Successful outcome of bone marrow transplantation BMT in malignant diseases is severely handicapped by susceptibility to infection and by a high rate of relapse. While quantitative aspects of the immune system generally return to normal within the firs! 3-4 months after BMT, the recovery of the qualitative immune function is delayed. Since interleukin-7 (IL-7) has growth-promoting and differentiating effects on pre-B cells and immature thymocytes, its role in the recovery of immune functions was investigated in (Balb/c x. C57/BL) FI mice (semiallogeneic BMT). After BMT, mice treated with human recombinant IL-7 showed a high increase in thymic cellularity, associated with a enhanced response to a mitogenic stimuTus compared with the controls, IL-7 significantly increased RAG1 expression (known as the gene that promoted V gene rdearrangement of the T-cell receptor (TCR) in the thymus). As a consequence of the RAG-1 expression, the rate of TCR gene rearrangement was accelerated as indicated by the first V8 (D)J arrangement signal at 15 days after BMT, and its magnitude gradually increased. In addition, the cytokine induced in the thymus an overexpression of mRNA IL-2 with correlation of high excretion of IL-2. Furthermore, the cytokine improved survival after challenging the mice with either the influenza virus or BCLl leukemia. IL-7 enhanced the GVL effect while decreasing the incidence of graft vs. host disease (GVHD). In conclusion, the present study is the first to show the effects of in vivoadministered rIL-7 on T cell maturation following BMT. Considering the RAG-1 expression and T cell receptor rearrangement, it seems acceptable that this cytokine could serve as a promoter of immune recovery boosting GVL while sparing GVHD after BMT. Our findings show IL-7 to be a promising medium for clinical application in BMT patients.