Stimulation of immune reconstitution by interleukin-7 after syngeneic bone marrow transplantation in mice

Abstract

Successful outcome of autologous bone marrow transplantation (BMT) 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 first 3-4 months after BMT, the recovery of qualitative immune functions is prolonged. 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 mice after syngeneic BMT (sBMT). After sBMT, mice treated with human recombinant IL-7 (rIL-7) showed an 11.9-fold increase in thymic cellularity associated with an enhanced response to a mitogenic stimulus compared with the controls. rIL-7 significantly increased RAG-1 expression and promoted V beta 8(D)J gene rearrangement of the T cell receptor in the thymus. Further, the cytokine boosted survival after challenge with influenza virus following sBMT. The finding that rIL-7 induces differentiation and proliferation of immature thymocytes and counteracts post-BMT immune deficiency makes it a promising medium for clinical application in BMT patients.