Biological and clinical implications of interleukin-7 and lymphopoiesis

Cytokines Cell Mol Ther. 1999 Mar;5(1):25-39.

Abstract

Interleukin 7 (IL-7) is a stromal cell-derived cytokine that stands out as being the only cytokine identified to date on which development of B and T lymphocytes is absolutely dependent. IL-7 functions primarily as a growth and antiapoptosis factor for B- and T-cell (alphabeta and gammadelta TCR+ cells) precursors, and is essential for differentiation of gammadelta TCR+ cells. IL-7 can function as a cofactor during myelopoiesis, and is capable of activating monocytes/macrophages and natural killer (NK) cells. Its receptor (IL-7R) is a heterodimer of an alpha chain that specifically binds IL-7 and the common gamma chain gammac that is also a component of the receptors for IL-2, IL-4, IL-9 and IL-15. The functions of IL-7 in normal lymphocyte development and activation have led to the demonstration of the ability of IL-7 to stimulate lymphopoiesis in lymphopenic mice, suggesting a possible clinical application of IL-7 in accelerating lymphoid reconstitution in lymphopenic patients. There have also been a number of preclinical studies pointing to the possible utility of IL-7 in antitumor clinical applications, and clinical trials involving IL-7 gene therapy of metastatic disease are underway. IL-7 has also been shown to promote engraftment of stem cells in mice receiving bone marrow transplants, pointing to a possible use of IL-7 in patients receiving bone marrow or peripheral blood stem cell transplants. Areas of IL-7 biology that are essentially unexplored include the mechanisms of regulation of the expression of IL-7 and IL-7Ralpha, as well as the mechanisms by which IL-7 is a growth and differentiation factor for gammadelta T cells but a growth factor only for alphabeta T cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • B-Lymphocytes / physiology*
  • Hematopoiesis / physiology
  • Humans
  • Interleukin-7 / chemistry
  • Interleukin-7 / physiology*
  • Interleukin-7 / therapeutic use*
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Receptors, Interleukin-7 / chemistry
  • T-Lymphocytes / physiology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Interleukin-7
  • Receptors, Interleukin-7