Effects of exogenous interleukin-7 on human thymus function

被引:110
作者
Okamoto, Y
Douek, DC
McFarland, RD
Koup, RA
机构
[1] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
[2] NCI, Dept Expt Transplantat & Immunol, Med Branch, NIH, Bethesda, MD 20892 USA
[3] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA
关键词
D O I
10.1182/blood.V99.8.2851
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 naive T-cell generation in immunocompromised patients. (C) 2002 by The American Society of Hematology.
引用
收藏
页码:2851 / 2858
页数:8
相关论文
共 71 条
[1]  
AbdulHai A, 1996, EXP HEMATOL, V24, P1416
[2]   Thymic atrophy in the mouse is a soluble problem of the thymic environment [J].
Aspinall, R ;
Andrew, D .
VACCINE, 2000, 18 (16) :1629-1637
[3]  
Blom B, 1999, BLOOD, V93, P3033
[4]  
Blom B, 1997, J IMMUNOL, V158, P3571
[5]  
Bolotin E, 1996, BLOOD, V88, P1887
[6]   Serum levels of IL-7 in bone marrow transplant recipients: relationship to clinical characteristics and lymphocyte count [J].
Bolotin, E ;
Annett, G ;
Parkman, R ;
Weinberg, K .
BONE MARROW TRANSPLANTATION, 1999, 23 (08) :783-788
[7]  
DADMARZ R, 1994, LYMPHOKINE CYTOK RES, V13, P349
[8]  
Dalloul AH, 1999, J IMMUNOL, V162, P5821
[9]   FUNCTIONAL-CHARACTERIZATION OF THE PROMOTER FOR THE HUMAN GERM-LINE T-CELL RECEPTOR J-ALPHA (TEA) TRANSCRIPT [J].
DECHASSEVAL, R ;
DEVILLARTAY, JP .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1993, 23 (06) :1294-1298
[10]   Changes in thymic function with age and during the treatment of HIV infection [J].
Douek, DC ;
McFarland, RD ;
Keiser, PH ;
Gage, EA ;
Massey, JM ;
Haynes, BF ;
Polis, MA ;
Haase, AT ;
Feinberg, MB ;
Sullivan, JL ;
Jamieson, BD ;
Zack, JA ;
Picker, LJ ;
Koup, RA .
NATURE, 1998, 396 (6712) :690-695