IL‐7 effect on immunological reconstitution after HSCT depends on MHC incompatibility

Abstract

Considerable progress has been recently accomplished in the management of patients who have undergone haplo‐incompatible haematopoietic stem cell transplantation (HSCT) in terms of intake and prevention of graft‐versus‐host disease. Nevertheless haplo‐incompatible HSCT is a procedure limited to a small number of patients because of the long‐lasting immunodeficiency that is responsible for more than 50% of deaths within the first 3 months. Interleukin (IL)‐7, which plays a unique and key role in T‐cell development both in the mouse and in the human, is particularly attractive for attempting to speed up T‐cell reconstitution. However, controversial results have been obtained after bone marrow graft in murine and primate models. To elucidate the impact of IL‐7 treatment, we have performed HSCT in irradiated murine recombination activating gene (RAG) immunodeficient recipients, using donors that exhibited increased major histocompatibilty complex (MHC) incompatibility. Although irradiation performed prior to HSCT lead to a profound defect in the thymic stromal cells responsible for IL‐7 production, IL‐7 treatment had no significant effect on immune reconstitution in the MHC compatible and partially compatible settings. Interestingly, in the MHC fully incompatible setting in which only one‐third of the recipients demonstrated active thymopoiesis, probably because of the rejection of donor cells by host natural killer cells, IL‐7 treatment had a beneficial effect on T‐cell development.