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Blood, 15 April 2002, Vol. 99, No. 8, pp. 2851-2858
IMMUNOBIOLOGY
Effects of exogenous interleukin-7 on human thymus
function
Yukari Okamoto,
Daniel C. Douek,
Richard D. McFarland, and
Richard A. Koup
From the 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; and the Center
for Biologics Evaluation and Research, Food and Drug Administration,
Rockville, MD.
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-  rearrangement and indicate the
potential use of IL-7 for enhancing de novo naïve T-cell
generation in immunocompromised patients.
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