Administration of interleukin-7 after allogeneic bone marrow transplantation improves immune reconstitution without aggravating graft-versus-host disease Journal Article

Authors: Alpdogan, O.; Schmaltz, C.; Muriglan, S. J.; Kappel, B. J.; Perales, M. A.; Rotolo, J. A.; Halm, J. A.; Rich, B. E.; van den Brink, M. R. M.
Article 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 donorderived 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. © 2001 by The American Society of Hematology.
Keywords: adolescent; controlled study; transplantation, homologous; nonhuman; t lymphocyte; t-lymphocytes; animal cell; mouse; animals; mice; immune system; interleukin 7; allogenic bone marrow transplantation; b lymphocyte; b-lymphocytes; mice, inbred strains; cytokines; immune response; thymus gland; newborn; graft versus host reaction; natural killer cell; t-lymphocyte subsets; monocyte; macrophage; memory cell; major histocompatibility complex; bone marrow transplantation; graft vs host disease; graft versus leukemia effect; interleukin-7; graft vs leukemia effect; interleukin 7 receptor; female; priority journal; article
Journal Title: Blood
Volume: 98
Issue: 7
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2001-10-01
Start Page: 2256
End Page: 2265
Language: English
DOI: 10.1182/blood.V98.7.2256
PUBMED: 11568014
PROVIDER: scopus
Notes: Export Date: 21 May 2015 -- Source: Scopus
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MSK Authors
  1. Jens Halm
    3 Halm
  2. Miguel-Angel Perales
    365 Perales
  3. Jimmy A Rotolo
    31 Rotolo
  4. Barry J Kappel
    28 Kappel