title: Administration of interleukin-7 after allogeneic bone marrow transplantation improves immune reconstitution without aggravating graft-versus-host disease.
abstract: Prolonged immunodeficiency after allogeneic bone marrow transplantation (BMT) causes significant morbidity and mortality from infection. This study examined in murine models the effects of interleukin-7 (IL-7) given to young and middle-aged (9-month-old) recipients of major histocompatibility complex (MHC)-matched or -mismatched allogeneic BMT. Although administration of IL-7 from day 0 to 14 after syngeneic BMT promoted lymphoid reconstitution, this regimen was ineffective after allogeneic BMT. However, IL-7 administration from day 14 (or 21) to 27 after allogeneic BMT accelerated restoration of the major lymphoid cell populations even in middle-aged recipients. This regimen significantly expanded donor-derived thymocytes and peripheral T cells, B-lineage cells in bone marrow and spleen, splenic natural killer (NK) cells, NK T cells, and monocytes and macrophages. Interestingly, although recipients treated with IL-7 had significant increases in CD4(+) and CD8(+) memory T-cell populations, increases in naive T cells were less profound. Most notable, however, were the observations that IL-7 treatment did not exacerbate graft-versus-host disease (GVHD) in recipients of an MHC-matched BMT, and would ameliorate GVHD in recipients of a MHC-mismatched BMT. Nonetheless, graft-versus-leukemia (GVL) activity (measured against 32Dp210 leukemia) remained intact. Although activated and memory CD4(+) and CD8(+) T cells normally express high levels of IL-7 receptor (IL-7R, CD127), activated and memory alloreactive donor-derived T cells from recipients of allogeneic BMT expressed little IL-7R. This might explain the failure of IL-7 administration to exacerbate GVHD. In conclusion, posttransplant IL-7 administration to recipients of an allogeneic BMT enhances lymphoid reconstitution without aggravating GVHD while preserving GVL.
authors.affiliation: Department of Medicine and Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: O
authors.initials: O
authors.lastname: Alpdogan
authors.forename: C
authors.initials: C
authors.lastname: Schmaltz
authors.forename: S J
authors.initials: SJ
authors.lastname: Muriglan
authors.forename: B J
authors.initials: BJ
authors.lastname: Kappel
authors.forename: M A
authors.initials: MA
authors.lastname: Perales
authors.forename: J A
authors.initials: JA
authors.lastname: Rotolo
authors.forename: J A
authors.initials: JA
authors.lastname: Halm
authors.forename: B E
authors.initials: BE
authors.lastname: Rich
authors.forename: M R
authors.initials: MR
authors.lastname: van den Brink
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology / Q000379:methods*; D016207:Cytokines / Q000187:drug effects; D006086:Graft vs Host Disease / Q000209:etiology; D020544:Graft vs Leukemia Effect; D007107:Immune System / Q000166:cytology / Q000187:drug effects*; D015851:Interleukin-7 / Q000008:administration & dosage*; D051379:Mice; D008815:Mice, Inbred Strains; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods
chemical_list: D016207:Cytokines; D015851:Interleukin-7