title: Effects of exogenous interleukin-7 on human thymus function.
abstract: Immune reconstitution is a critical component of recovery after treatment of human immunodeficiency virus (HIV) infection, cancer chemotherapy, and hematopoietic stem cell transplantation. The ability to enhance T-cell production would benefit such treatment. We examined the effects of exogenous interleukin-7 (IL-7) on apoptosis, proliferation, and the generation of T-cell receptor rearrangement excision circles (TRECs) in human thymus. Quantitative polymerase chain reaction demonstrated that the highest level of TRECs (14 692 copies/10 000 cells) was present in the CD1a(+)CD3(-)CD4(+)CD8(+) stage in native thymus, suggesting that TREC generation occurred following the cellular division in this subpopulation. In a thymic organ culture system, exogenous IL-7 increased the TREC frequency in fetal as well as infant thymus, indicating increased T-cell receptor (TCR) rearrangement. Although this increase could be due to the effect of IL-7 to increase thymocyte proliferation and decrease apoptosis of immature CD3(-) cells, the in vivo experiments using NOD/LtSz-scid mice given transplants of human fetal thymus and liver suggested that IL-7 can also directly enhance TREC generation. Our results provide compelling evidence that IL-7 has a direct effect on increasing TCR-alphabeta rearrangement and indicate the potential use of IL-7 for enhancing de novo naïve T-cell generation in immunocompromised patients.
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases and Department of Experimental Transplantation and Immunology, Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: Richard D
authors.initials: RD
authors.lastname: McFarland
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005333:Fetus; D015329:Gene Rearrangement, T-Lymphocyte / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D015851:Interleukin-7 / Q000008:administration & dosage / Q000494:pharmacology*; D019891:Leukopoiesis / Q000187:drug effects; D008099:Liver / Q000166:cytology; D016131:Lymphocyte Subsets; D051379:Mice; D016513:Mice, SCID; D020395:Receptors, Interleukin-7 / Q000032:analysis; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D016378:Tissue Transplantation; D014183:Transplantation, Heterologous
chemical_list: D015851:Interleukin-7; D020395:Receptors, Interleukin-7