IL-7 effect on immunological reconstitution after HSCT depends on MHC incompatibility.
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.
André-Schmutz
Isabelle
I
INSERM U 429, Hôpital Necker Enfants Malades, Paris, France. andre-schmutz@necker.fr
Bonhomme
Delphine
D
Yates
Frank
F
Malassis
Michèle
M
Selz
Françoise
F
Fischer
Alain
A
Cavazzana-Calvo
Marina
M
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
D015851:Interleukin-7; D011994:Recombinant Proteins