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

J Immunol. 2003 Jul 15;171(2):645-54. doi: 10.4049/jimmunol.171.2.645.

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 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD34 / biosynthesis
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Biological Availability
  • Cell Differentiation / immunology
  • Cell Division / immunology
  • Cell Survival / immunology
  • Cells, Cultured
  • Dexamethasone / antagonists & inhibitors
  • Dexamethasone / pharmacology
  • Fetus
  • HIV Infections / genetics
  • HIV Infections / immunology
  • HIV Infections / pathology
  • Humans
  • Interleukin-7 / administration & dosage*
  • Interleukin-7 / pharmacokinetics
  • Interleukin-7 / pharmacology*
  • Intracellular Fluid / immunology
  • Intracellular Fluid / metabolism
  • Mice
  • Mice, SCID
  • Organ Culture Techniques
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Stem Cells / cytology
  • Stem Cells / immunology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Thymus Gland / cytology*
  • Thymus Gland / immunology*
  • Thymus Gland / pathology
  • Thymus Gland / virology
  • Up-Regulation / immunology

Substances

  • Antigens, CD34
  • Interleukin-7
  • Proto-Oncogene Proteins c-bcl-2
  • Dexamethasone