Effects of exogenous interleukin-7 on human thymus function.
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.
Okamoto
Yukari
Y
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.
Douek
Daniel C
DC
McFarland
Richard D
RD
Koup
Richard A
RA
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
D015851:Interleukin-7; D020395:Receptors, Interleukin-7