Effects of exogenous interleukin-7 on human thymus function

• Published in: Blood 2002-04, Vol.99 (8), p.2851-2858
• Main Authors: Okamoto, Yukari, Douek, Daniel C., McFarland, Richard D., Koup, Richard A.
• Format: Article
• Language: English
• Subjects: Adult; Animals; Apoptosis - drug effects; Biological and medical sciences; Cell Division - drug effects; Fetus; Gene Rearrangement, T-Lymphocyte - drug effects; Humans; Immunopathology; Immunophenotyping; Immunotherapy (general aspects); Infant; Infant, Newborn; Interleukin-7 - administration & dosage; Interleukin-7 - pharmacology; Leukopoiesis - drug effects; Liver - cytology; Lymphocyte Subsets; Medical sciences; Mice; Mice, SCID; Receptors, Interleukin-7 - analysis; Thymus Gland - cytology; Thymus Gland - drug effects; Thymus Gland - physiology; Tissue Transplantation; Transplantation, Heterologous
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V99.8.2851

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-αβ rearrangement and indicate the potential use of IL-7 for enhancing de novo naı̈ve T-cell generation in immunocompromised patients.