title: 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.
authors.affiliation: INSERM U 429, Hôpital Necker Enfants Malades, Paris, France. andre-schmutz@necker.fr
authors.forename: Isabelle
authors.initials: I
authors.lastname: André-Schmutz
authors.forename: Delphine
authors.initials: D
authors.lastname: Bonhomme
authors.forename: Frank
authors.initials: F
authors.lastname: Yates
authors.forename: Michèle
authors.initials: M
authors.lastname: Malassis
authors.forename: Françoise
authors.initials: F
authors.lastname: Selz
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Marina
authors.initials: M
authors.lastname: Cavazzana-Calvo
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D015851:Interleukin-7 / Q000627:therapeutic use*; D008198:Lymph Nodes / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
chemical_list: D015851:Interleukin-7; D011994:Recombinant Proteins