Molecular and functional evidence for activity of murine IL-7 on human lymphocytes

Exp Hematol. 2006 Sep;34(9):1133-42. doi: 10.1016/j.exphem.2006.05.001.


Although interleukin-7 (IL-7) is essential for human and murine lymphopoiesis and homeostasis, clear disparities between these species regarding the role of IL-7 during B-cell development suggest that other, subtler differences may exist. One basic unsolved issue of IL-7 biology concerns cross-species activity, because in contrast to the human ortholog, the ability of murine (m)IL-7 to stimulate human cells remains unresolved. Establishing whether two-way cross-species reactivity occurs is fundamental for evaluating the role of IL-7 in chimeric human-mouse models, which are the most versatile tools for studying human lymphoid development and disease in vivo. Here, we show that mIL-7 triggers the same signaling pathways as human (h)IL-7 in human T cells, promoting similar changes in viability, proliferation, size, and immunophenotype, even at low concentrations. This ability is not confined to T cells, because mIL-7 mediates cell growth and protects human B-cell precursors from dexamethasone-induced apoptosis. Importantly, endogenous mIL-7 produced in the mouse thymic microenvironment stimulates human T cells, because their expansion in chimeric fetal thymic organ cultures is inhibited by a mIL-7-specific neutralizing antibody. Our results demonstrate that mIL-7 affects human lymphocytes and indicate that mouse models of human lymphoid development and disease must integrate the biological effects of endogenous IL-7 on human cells.

Publication types

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

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cell Line
  • Cell Proliferation / drug effects
  • Coculture Techniques
  • Dexamethasone / pharmacology
  • Homeostasis / immunology*
  • Humans
  • Interleukin-7 / immunology*
  • Interleukin-7 / pharmacology
  • Lymphopoiesis / immunology*
  • Mice
  • Models, Immunological
  • Organ Culture Techniques
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Species Specificity
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / embryology
  • Thymus Gland / immunology*


  • Anti-Inflammatory Agents
  • Interleukin-7
  • Dexamethasone