Effects of IL-7 on early human thymocyte progenitor cells in vitro and in SCID-hu Thy/Liv mice

Laura A. Napolitano, Cheryl A. Stoddart, Mary Beth Hanley, Eric Wieder, Joseph M. McCune

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

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 CD34highCD5+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.

Original languageEnglish (US)
Pages (from-to)645-654
Number of pages10
JournalJournal of Immunology
Volume171
Issue number2
DOIs
StatePublished - Jul 15 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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