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Br J Haematol ; 126(6): 844-51, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15352989

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.


Subject(s)
Hematopoietic Stem Cell Transplantation , Interleukin-7/therapeutic use , Major Histocompatibility Complex/immunology , Animals , B-Lymphocytes/immunology , Disease Models, Animal , Female , Lymph Nodes/immunology , Male , Mice , Mice, Inbred Strains , Recombinant Proteins/therapeutic use , T-Lymphocytes/immunology , Thymus Gland/immunology
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