Effects of IL-7 on early human thymocyte progenitor cells in vitro and in SCID-hu Thy/Liv mice.
IL-7 is a critical component of thymopoiesis in animals and has recently been shown to play an important role in T cell homeostasis. Although there is increasing interest in the use of IL-7 for the treatment of lymphopenia caused by the HIV type 1, evidence that IL-7 may accelerate HIV replication has raised concerns regarding its use in this setting. We sought to identify the effects of IL-7 on human thymocyte survival and to determine the impact of IL-7 administration on in vivo HIV infection of the human thymus. Using in vitro analysis, we show that IL-7 provides potent anti-apoptotic and proliferative signals to early thymocyte progenitors. Analysis of CD34(+) subpopulations demonstrates that surface IL-7 receptor is expressed on most CD34(high)CD5(+)CD1a(-) thymocytes and that this subpopulation appears to be one of the earliest maturation stages responsive to the effects of IL-7. Thus, IL-7 provides survival signals to human thymocytes before surface expression of CD1a. CD4(+)CD8(+) thymocytes are relatively unresponsive to IL-7, although IL-7 protects these cells from dexamethasone-induced apoptosis. IL-7 has a predominantly proliferative effect on mature CD4(+)CD3(+)CD8(-) and CD8(+)CD3(+)CD4(-) thymocytes. In contrast to the in vitro findings, we observe that in vivo administration of IL-7 to SCID-hu Thy/Liv mice does not appear to enhance thymocyte survival nor does it appear to accelerate HIV infection. Given the growing interest in the use of IL-7 for the treatment of human immunodeficiency, these findings support additional investigation into its in vivo effects on thymopoiesis and HIV infection.
Napolitano
Laura A
LA
Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94141, USA. lnapoli@itsa.ucsf.edu
Stoddart
Cheryl A
CA
Hanley
Mary Beth
MB
Wieder
Eric
E
McCune
Joseph M
JM
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001682:Biological Availability; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005333:Fetus; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006801:Humans; D015851:Interleukin-7 / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009924:Organ Culture Techniques; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D013234:Stem Cells / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015854:Up-Regulation / Q000276:immunology
D018952:Antigens, CD34; D015851:Interleukin-7; D019253:Proto-Oncogene Proteins c-bcl-2; D003907:Dexamethasone